Σάββατο, 15 Δεκεμβρίου 2018

Metformin Affects Heme Function as a Possible Mechanism of Action

Metformin elicits pleiotropic effects that are beneficial for treating diabetes, and as well as particular cancers and aging. In spite of its importance, a convincing and unifying mechanism to explain how metformin operates is lacking. Here we describe investigations into the mechanism of metformin action through heme and hemoprotein(s). Metformin suppresses heme production by 50% in yeast, and this suppression requires mitochondria function, which is necessary for heme synthesis. At high concentrations comparable to those in the clinic, metformin also suppresses heme production in human erythrocytes, erythropoietic cells and hepatocytes by 30-50%; the heme-targeting drug artemisinin operates at a greater potency. Significantly, metformin prevents oxidation of heme in three protein scaffolds, cytochrome c, myoglobin and hemoglobin, with Kd values < 3 mM suggesting a dual oxidation and reduction role in the regulation of heme redox transition. Since heme- and porphyrin-like groups operate in diverse enzymes that control important metabolic processes, we suggest that metformin acts, at least in part, through stabilizing appropriate redox states in heme and other porphyrin-containing groups to control cellular metabolism.



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Mapping Oat Crown Rust Resistance Gene Pc45 Confirms Association with PcKM

Molecular mapping of crown rust resistance genes is important to effectively utilize these genes and improve breeding efficiency through marker-assisted selection. Pc45 is a major race-specific crown rust resistance gene initially identified in the wild hexaploid oat Avena sterilis in the early 1970s. This gene was transferred to cultivated oat (Avena sativa) and has been used as a differential for identification of crown rust races since 1974. Previous research identified an association between virulence to Pc45 and PcKM, a crown rust resistance gene in the varieties 'Kame' and 'Morton'. This study was undertaken to reveal the relationship between Pc45 and PcKM. Pc45 was studied in the crosses 'AC Morgan'/Pc45 and 'Kasztan'/Pc45, where Pc45 is the differential line carrying Pc45. F2 progenies and F2:3 families of both populations were inoculated with the crown rust isolate CR258 (race NTGG) and single gene segregation ratios were observed. SNP markers for PcKM were tested on these populations and linkage maps were generated. In addition, 17 newly developed SNP markers identified from genotyping-by-sequencing (GBS) data were mapped in these two populations, plus another three populations segregating for Pc45 or PcKM. Pc45 and PcKM mapped to the same location of Mrg08 (chromosome 12D) of the oat chromosome-anchored consensus map. These results strongly suggest that Pc45 and PcKM are the same resistance gene, but allelism (i.e. functionally different alleles of the same gene) or tight linkage (i.e. two tightly linked genes) cannot be ruled out based on the present data.



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Cover Image

Journal of Oral Rehabilitation Cover Image

The cover image, by Ariyan Mottaghi et al., is based on the Review Article Is there a higher prevalence of tinnitus in patients with temporomandibular disorders? A systematic review and meta‐analysis DOI: 10.1111/joor.12706.




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Issue Information



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Interneuron NMDA receptors change the gear of motor learning in the cerebellar machine



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Development of somatic markers guiding decision-making along adolescence

Publication date: Available online 15 December 2018

Source: International Journal of Psychophysiology

Author(s): Serra Sandor, Hakan Gürvit



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Distinct neural responses to social and semantic violations: An N400 study

Publication date: Available online 14 December 2018

Source: International Journal of Psychophysiology

Author(s): Natalie R. Weimer, Sheri L. Clark, Antonio L. Freitas

Abstract

We investigated event-related brain potential correlates of encountering context-incongruent social information. Building on evidence that information semantically incongruent with its context elicits an N400 response (a prominent negative-going deflection in the ongoing electroencephalogram; EEG), we hypothesized that statements incongruent (relative to congruent) with basic standards of amicable treatment by others (e.g., "Your friend breaks your computer and then laughs [apologizes]") would elicit larger-amplitude N400 responses. EEG was recorded from N = 20 undergraduates while they viewed 106 semantic-dimension and 106 social-dimension sentences. We obtained the classic N400 effect to semantic violations, but we did not observe greater N400 amplitudes to incongruent than to congruent social-dimension sentences. Our findings of N400 modulation by semantic violations but not social norm violations help clarify potential boundary conditions for eliciting the N400.



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Human factors and the 'next generation' airway trolley.

Related Articles

Human factors and the 'next generation' airway trolley.

Anaesthesia. 2018 Dec 14;:

Authors: Chrimes N, Bradley WPL, Gatward JJ, Weatherall AD

PMID: 30548998 [PubMed - as supplied by publisher]



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The effects of a 12-week jump rope exercise program on abdominal adiposity, vasoactive substances, inflammation, and vascular function in adolescent girls with prehypertension

Abstract

Introduction

Childhood obesity is strongly associated with cardiovascular disease (CVD) development. It is necessary to combat unfavorable outcomes of obesity at a young age by utilizing effective interventions, such as exercise.

Purpose

We sought to examine the effects of a jump rope exercise program on CVD risk factors, including body composition, vasoactive substances, inflammation, and vascular function in prehypertensive adolescent girls.

Methods

Forty girls (age 14–16) were recruited and randomly assigned to a jump rope exercise group (EX, n = 20) or control group (CON, n = 20). Body composition, nitrate and nitrite levels, endothelin-1 (ET-1), C-reactive protein (CRP), systolic blood pressure and diastolic blood pressure (SBP, DBP), and arterial stiffness were measured before and after 12 weeks.

Results

There were significant group by time interactions following the 12-week program for body composition (from 33.8 ± 3.6 to 30.2 ± 3.1%), central adiposity (from 86.4 ± 4 to 83.3 ± 5 cm), SBP (from 126 ± 3.3 to 120 ± 2.1 mmHg), and brachial-to-ankle pulse wave velocity (from 8.2 ± 1.0 to 7.4 ± 0.2 m/s). Nitrate/nitrite levels increased (from 54.5 ± 5.1 to 57.2 ± 5.2 µmol) along a reduction in CRP levels (from 0.5 ± 0.4 to 0.2 ± 0.1 mg/L). There were no significant changes in ET-1 (P = 0.22).

Conclusions

These findings indicate that jump rope exercise may be an effective intervention to improve these CVD risk factors in prehypertensive adolescent girls. Jumping rope is an easily accessible exercise modality that may have important health implications for CVD prevention in younger populations.



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Regulation of asymmetries in the kinetics and protein numbers of bacterial gene expression

Publication date: Available online 14 December 2018

Source: Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms

Author(s): Sofia Startceva, Vinodh K. Kandavalli, Ari Visa, Andre S. Ribeiro

Abstract

Genetic circuits change the status quo of cellular processes when their protein numbers cross thresholds. We investigate the regulation of RNA and protein threshold crossing propensities in Escherichia coli. From in vivo single RNA time-lapse microscopy data from multiple promoters, mutants, induction schemes and media, we study the asymmetry and tailedness (quantified by the skewness and kurtosis, respectively) of the distributions of time intervals between transcription events. We find that higher thresholds can be reached by increasing the skewness and kurtosis, which is shown to be achievable without affecting mean and coefficient of variation, by regulating the rate-limiting steps in transcription initiation. Also, they propagate to the skewness and kurtosis of the distributions of protein expression levels in cell populations. The results suggest that the asymmetry and tailedness of RNA and protein numbers in cell populations, by controlling the propensity for threshold crossing, and due to being sequence dependent and subject to regulation, may be key regulatory variables of decision-making processes in E. coli.



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Is it time to depart from dichotomization in ALS diagnosis?

Publication date: Available online 15 December 2018

Source: Clinical Neurophysiology

Author(s): Hiroyuki Nodera



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Eccentric Arm Cycling: A Potential Exercise for Wheelchair Users

Publication date: Available online 14 December 2018

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Lydia L.M. Lytle, Jennifer L. Dannenbring, Matthew A. Kilgas, Steven J. Elmer

Abstract
Objective

We compared metabolic, cardiorespiratory, and perceptual responses to acute eccentric (ECCarm) and traditional concentric (CONarm) arm cycling in a cohort of wheelchair users.

Design

Single-group repeated measures.

Setting

Exercise physiology laboratory.

Participants

A convenience sample of seven manual wheelchair users (45±15yrs; 87±21kg; 1.8±0.1m; time in wheelchair 17±14yrs) volunteered.

Interventions

Participants performed 5min trials of eccentric and concentric arm cycling at 1) iso-metabolic rate (35% of peak oxygen consumption) and 2) iso-power output (80W). Exercise trials were performed on an eccentric/concentric arm cycle ergometer that integrated with a personal wheelchair.

Main Outcome Measures

Primary measures included power output, oxygen consumption, heart rate, ventilation, blood lactate, and perceived exertion. Secondary measures assessed included perceived muscle soreness, likability, frequency of use, and duration of use.

Results

At iso-metabolic rate, power production during ECCarm was ∼3x greater than CONarm (80±36 vs. 26±10W; P<0.01). When exercising at iso-power output, oxygen consumption during ECCarm was ∼1/2 that of CONarm (0.66±0.15 vs 1.30±0.65L/min; P=0.03). Heart rate and perceived exertion were also substantially lower during ECCarm (both P<0.05). Muscle soreness assessed 24-72h post-exercise was minimal (<1.0cm). Preference scores and anticipated frequency and duration of use did not differ between ECCarm and CONarm (all P>0.05).

Conclusion

ECCarm provided a metabolically efficient (high-force, low energy cost) and usable (wheelchair accessible, safe, likable) exercise for wheelchair users. Implementation of ECCarm with this population is promising but additional research is needed to confirm this possibility.



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Systemwide clinical assessment of functioning based on the International Classification of Functioning, Disability and Health (ICF) in China: Interrater reliability, convergent, known group, and predictive validity of the ICF Generic-6

Publication date: Available online 14 December 2018

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Shouguo Liu, Jan D. Reinhardt, Xia Zhang, Cristina Ehrmann, Wenzhi Cai, Birgit Prodinger, Shan Liu, Jianan Li

Abstract
Objective

To validate the ICF Generic-6 in daily routine clinical practice in Mainland China. Specific objectives were to a) analyse the interrater reliability, b) convergent validity, c) known group validity and d) predictive validity of the ICF Generic-6.

Design

Multi-centre prospective cohort study.

Setting

50 hospitals from 20 provinces of Mainland China.

Participants

4510 patients from departments of Rehabilitation, Orthopaedics, Neurology, Cardiology, Pneumology, and Cerebral Surgery of the participating hospitals with different health condition were included in this study.

Intervention

Not applicable.

Main outcome measure

The assessment was undertaken by nurses with ICF Generic-6 in combination with a numeric rating scale. Interrater reliability was evaluated with intraclass correlation coefficients (ICC). Convergent validity was evaluated with Spearman correlation coefficients between ICF Generic-6 and SF-12 items. Known group-validity was examined by comparing discharge scores between different discharge destinations. Predictive validity was determined by employing ICF Generic-6 baseline scores for estimating length of hospital stay with a loglogistic survival model with gamma shared frailty and cost of in-hospital treatment with a mixed effects generalized linear regression model of the gamma family.

Principle finding

The interrater reliability of items and score of ICF Generic-6 was good with ICCs ranging from 0.67 to 0.87. ICF Generic-6 items were further correlated with respective SF-12 items. Discharge scores of patients differed significantly by discharge destination. The ICF Generic-6 admission score was a significant predictor of length of stay and treatment cost.

Conclusions

The ICF Generic-6 administered in combination with a 0 to 10 numeric rating scale is a reliable and valid tool for the collection of minimal information on functioning across various clinical settings.



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Residential Mobility and Flourishing Among United States School-Age Children, 2011/2012 National Survey of Children’s Health

Abstract

Objectives To investigate the association of residential mobility with flourishing among school-age children. Methods Data from the 2011/2012 National Survey of Children's Health were used to examine parent/caregiver-reported information on flourishing and residential mobility for children age 6–17 (N = 63,333). Residential mobility was the number of times the child moved categorized as: none, 1–2, and 3+. Children who were reported to show interest/curiosity, finish tasks, stay calm/in control, care about doing well in school, and do all homework were coded as flourishing. Sex-specific multivariable models were used to model the relative risk of mobility on flourishing. Interactions of mobility with age and poverty were tested. Results Among US school-age children, 22% had no moves, 39% had 1–2 moves and 39% had 3+ moves in their lifetime. Nearly half (45%) were flourishing. Both boys and girls who moved 3+ times were less likely to flourish compared to children with no moves. Among poor boys moving 3+ times was associated with less flourishing (aRR 0.83, 95% CI 0.71, 0.98) with no association for non-poor boy. Among girls the pattern was reversed (aRR 0.88, 95% CI 0.81, 0.95 for non-poor girls and no association for poor girls). Conclusions for Practice Residential mobility may lead to lower rates of flourishing. The patterns, when stratified by age or poverty, are different for boys and girls.



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Vitamin D Supplements Don’t Reduce Cancer Incidence

12/13/2018

In the largest-ever randomized trial testing vitamin D for cancer prevention, the supplement did not lower the risk of developing cancer. The Vitamin D and Omega-3 Trial (VITAL) includes a nationally representative sample of nearly 26,000 participants.

Indian Journal of Nephrology (Indian J Nephrol)

ORIGINAL ARTICLES 

Epidemiology and outcomes of acute kidney injury in critically ill: Experience from a tertiary care center Highly accessed articlep. 413
PS Priyamvada, R Jayasurya, Vijay Shankar, S Parameswaran
DOI:10.4103/ijn.IJN_191_17  
There is only limited information on the epidemiology and outcomes of acute kidney injury (AKI) in critically ill patients from low- and middle-income countries. This study aims to identify the etiology, short-term outcomes, and determinants of mortality in patients with AKI admitted to multiple medical and surgical Intensive Care Units (ICU's) in a tertiary care center. The study also aims to compare the clinical characteristics and outcomes of community-acquired AKI (CAAKI) and hospital-acquired AKI (HAAKI). A prospective, observational study was done from June 2013 to October 2015. All patients over 18 years with AKI admitted in various medical and surgical ICU's seeking nephrology referral were included. AKI was defined according to KDIGO criteria. The follow-up period was 30 days. A total of 236 patients were recruited from five medical and nine surgical ICU's. Majority (73.3%) were males. About 53.38% patients had CAAKI, whereas 46.61% had HAAKI. The predominant etiologies for AKI were sepsis (22.4%), trauma due to road traffic accidents (21.18%), acute abdomen (perforation, acute pancreatitis, bowel gangrene, intestinal obstruction and cholangitis) (18.64%), and cardiac diseases (10.59%). Sepsis and acute abdomen were the most common causes of CAAKI, whereas trauma and cardiac causes were the predominant causes of HAAKI (P < 0.05). Patients with HAAKI were younger, admitted in surgical units, had lower SOFA scores, lower serum creatinine, lesser need for dialysis, longer hospital stay, and earlier stages of AKI compared to patients with CAAKI (P < 0.05). The 30-day mortality was 52.54%. The mortality was not different between CAAKI and HAAKI (56.3% vs. 48.18%; relative risk = 0.86: 95% confidence interval 0.67–1.1). The mortality was similar across different stages of AKI.
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Skin microcirculatory changes in relation to arteriovenous fistula maturationp. 421
Siew Cheng Chai, Wan Azman Wan Sulaiman, Arman Zaharil Mat Saad, Aida Hanum Rasool, Amran Ahmed Shokri
DOI:10.4103/ijn.IJN_402_17  
Maturation of arteriovenous fistula (AVF) involves complex vascular remodeling. In this study, we evaluated the changes of skin microvascular perfusion over the extremity with AVF maturation using the laser Doppler fluximetry (LDF). A total of 45 patients with chronic kidney disease, Stages IV–V, were included; they had undergone AVF creation from July 2014 to June 2016 at our institute. The measurement of skin microvascular perfusion was accomplished proximal and distal to the fistula anastomosis site: pre- and post-operative day 1, week 2, week 6, and week 12. Thirty-two patients with mean age of 55.6 had achieved AVF maturation. There were 40.6% radial-based and 59.4% brachial-based AVF. There was a 32.8% reduction of mean skin perfusion distal to the fistula by day 1 compared to the baseline perfusion; however, perfusion increased 47% by week 2 compared to day 1 and no dramatic change was subsequently noted. There was an increase of mean skin perfusion, proximal to fistula anastomosis, over 12 weeks with 35.8% at day 1 from the baseline. However, the changes of the mean skin perfusion were not statistically significant. There was no significant relation of skin perfusion changes with the type of fistula, diabetes mellitus, hypertension, and hyperlipidemia. LDF successfully detected the subclinical change of skin microvascular perfusion in relation to AVF creation. Reduction of skin perfusion distal to the fistula suggests that in patients with existing perfusion inadequacy of extremities, they may experience ischemic symptoms as early as day 1 postoperation, and require close monitoring for distal limb ischemic-related complications.
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Urinary neutrophil gelatinase-associated lipocalin and urinary soluble CXCL16 as biomarkers of activity in pediatric lupus nephritisp. 427
MA El-Gamasy, W El-Naghy
DOI:10.4103/ijn.IJN_265_17  
One of the challenges of treating patients with lupus nephritis (LN) is to assess disease activity. The aim of this study was to measure the urinary neutrophil gelatinase-associated lipocalin (uNGAL) and urinary soluble chemokine (C-X-C motif) ligand 16 (CXCL16) levels in children and adolescents with systemic lupus erythematosus (SLE) and investigate whether they are elevated in active LN. This study was conducted on 80 patients diagnosed as SLE by the Systemic Lupus International Collaborating Clinics criteria and 60 apparently healthy individuals as controls. Global and renal disease activities were evaluated by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and renal SLEDAI, respectively. uNGAL and urinary CXCL16 were measured for all participants by ELISA. Renal biopsy was done for all cases at initial diagnosis and was graded using ISN/RPS classification. uNGAL and CXCL16 were higher in patients than in the controls (8.9 ± 3.56 ng/dl and 1067 ± 367 ug/L vs. 2.26 ± 1.95 ng/dl and 471 ± 106 ug/L, respectively). uNGAL had higher sensitivity and specificity than urinary CXCL16 as predictor of LN (95% and 90% vs. 85% and 80%, respectively). There was significant positive correlations between uNGAL levels, 24-h urinary proteins (r = 0.732, P = 0.001), and SLEDAI (r = 0.359, P = 0.001). There was also significant positive correlations between urinary CXCL16 levels, 24-h urinary proteins (r = 0.47, P = 0.001), and SLEDAI (r = 0.17, P = 0.001). uNGAL and CXCL16 were reliable indicators of the activity of LN.
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Optimization of treatment modality in elderly end-stage renal disease population: Peritoneal dialysis versus transplantp. 433
A Kaul, MR Behera, R Kishore, B Karthikeyan, DS Bhadauria, P Mishra, N Prasad, A Gupta, RK Sharma
DOI:10.4103/ijn.IJN_305_17  
Despite kidney transplantation (KT) being considered as the best treatment modality for end-stage renal disease (ESRD), patient and graft survival in the elderly population is poorer than younger individuals. Many authors argue that prolonged life expectancy outweighs the risk of remaining on dialysis, but few studies had compared the treatment modalities, especially with peritoneal dialysis (PD). A retrospective study was conducted at a tertiary care institute to compare outcome of elderly ESRD patients, who received KT with those continued on PD; and to evaluate the predictors of patient survival. Patient survival at 1 year was (76.2% vs. 91.1%); 5 years (53.7% vs. 21.8%); and 10 years (35.6% vs. 0.00%) among KT and PD population, respectively. Infection was the most common cause of death among KT group (35 [41.2%] vs. 34 [28.2%]) while cardiovascular mortality in PD group (55 [46.2%] vs. 7 [8.2%]). Technique survival at 1, 5, and 10 years in PD group was 92.8%, 58.5%, and 0%, respectively. Similarly, graft survival at 1, 5, and 10 years in KT group was 98.7%, 90.2%, and 90.2%, respectively. Multivariate analysis showed body mass index (BMI) (hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.82–0.93, p < 0.001), and albumin (HR 0.55, 95% CI 0.37–0.80, p = 0.002) were significant predictors of survival. In the 1st year, patient survival was better in PD than KT, but after adjustment for BMI and albumin, both short-term and long-term survival in elderly KT group was better than that of PD. Hence, elderly ESRD patients should not be barred from KT just because of age.
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Role of blood oxygen level-dependent MRI in differentiation of acute renal allograft dysfunctionp. 441
Hira Lal, Ezaz Mohamed, Neelam Soni, Priyank Yadav, Manoj Jain, Dharmendra Bhadauria, Anupma Kaul, Narayan Prasad, Amit Gupta, RK Sharma
DOI:10.4103/ijn.IJN_43_18  
Early graft dysfunction after renal transplantation manifests as acute rejection (AR) or acute tubular necrosis (ATN). Blood oxygen level-dependent (BOLD) magnetic resonance (MR) imaging is a noninvasive method of assessing tissue oxygenation, which may be useful for predicting acute allograft dysfunction. This was a prospective study involving 40 patients scheduled for renal transplantation from August 2012 to August 2014. In addition, 15 healthy donors were also enrolled in this study. All recipients underwent BOLD MR imaging (MRI) and R2* mapping 10–20 days after transplant, and additionally within 48 h of biopsy if there was any evidence of graft dysfunction. The healthy donors underwent BOLD MRI 1–2 days before surgery. The biopsies were grouped into AR, ATN, and no evidence of AR or ATN. The mean medullary R2*, cortical R2*, corticomedullary gradient, and medullary: cortical R2* ratio were compared between groups using one-way analysis of variance. Spearman's correlation and multinomial linear regression were applied to determine the influence factors of R2* value. Overall, nine patients had graft dysfunction. Six were reported as AR, two as ATN, and one as no evidence of ATN or rejection. The mean medullary and cortical R2* were significantly higher in ATN group compared with AR and normal group, whereas the mean medullary and cortical R2* of AR group were significantly lower than normal group. The corticomedullary gradient of AR group was significantly lower compared with ATN and normal group. Medullary R2*:cortical R2* ratio was significantly lower in AR group compared with normal group. No significant difference was noted between the 15 donors and patients with normal graft function. R2* values on BOLD MRI are significantly decreased in AR allografts and increased in an early stage of ATN allografts, suggesting that BOLD MRI can become a valuable tool for discriminating between AR and ATN.
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Prevalence and clinical correlates of white coat effect in patients with chronic kidney disease and the role of automated blood pressure device in its assessmentp. 448
Srinivas Shenoy, Shankar Prasad Nagaraju, Nileshwar R Rau, Ravindra A Prabhu, Uday Venkat Mateti, Dharshan Rangaswamy, Indu R Rao, Karan Saraf
DOI:10.4103/ijn.IJN_418_17  
Context: Hypertension in chronic kidney disease (CKD) is an important modifiable cardiovascular risk factor. Patients with CKD can have clinically significant white coat effect (WCE), making routine clinic blood pressure (BP) measurements an unreliable indicator of actual BP control. Automated BP monitoring is useful in identifying WCE. The utility of automated BP monitoring has seldom been part of clinical practice in developing countries. Aim: The goal of this study was to estimate the prevalence and determinants of WCE in adult patients with CKD in an outpatient setting using an automated BP device. Materials and Method: In this prospective observational study, patients with CKD attending the nephrology clinic over a period of 6 months (January 2016 to July 2016), who were suspected to have WCE by the treating physician, were assigned to measurement of BP by both the standardized manual BP recording by a single nephrologist and with automated machine as per a defined protocol. Clinical, demographic characters that would influence outcomes were also studied. Results: Among 118 patients with CKD with suspected WCE, 57.6% showed WCE. The mean systolic and diastolic BPs were significantly lower with automated machine when compared with manual BP recordings in patients with WCE (p = 0.04). WCE was seen in all stages of CKD. Occurrence of WCE in CKD was not dependent on factors such as old age, sex, diabetes mellitus, or smoking status in our study. Conclusion:WCE is a highly prevalent and underdiagnosed entity in patients with CKD. Automated machine is a useful and time-saving tool in detection of WCE in patients with CKD attending the outpatient clinic and guide management.
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Acute pyelonephritis: A single-center experiencep. 454
L Umesha, SM Shivaprasad, EN Rajiv, MM Satish Kumar, V Leelavathy, CG Sreedhara, MR Niranjan
DOI:10.4103/ijn.IJN_219_16  
Acute pyelonephritis (APN), although a common clinical entity, still not much is known about the clinical profile in the Indian scenario. We prospectively collected clinical, biochemical, and radiological data of patients hospitalized with a diagnosis of APN from March 2014 to June 2016. A total of 296 cases were included in the study. Mean age was 53.85 ± 9.78 years. Male to females ratio was 1.93:1. Among the risk factors recognized for complicated pyelonephritis (PN), diabetes mellitus (DM) (54.4%) was the most common factor followed by renal calculi (14.4%), benign prostatic hyperplasia (6.7%), immunocompromised state (3.3%), stricture urethra and meatal stenosis (3.3%), and neurogenic bladder (2%). Urinary culture was negative in 153 (51.7%) and positive in 143 patient (48.3%). Most common organism isolated was Escherichia coli (29.7%), followed by Klebsiella pneumoniae (5.4%), pseudomonas (5.4%), Enterococcus (4.4%), and Proteus in 10 (3.4%). Serum creatinine of more than 1.5 mg/dl at admission was seen in 96.3% patients; 40% of them had underlying chronic kidney disease with DM being the most common. Multiorgan dysfunction either at admission or during the course in hospital stay was seen in 31.8% patients. Twelve (2%) had emphysematous PN. Six patients had Class II, 4 had Class III, 1 with Class I, and another with Class IV. A total of 18 deaths were noted (6.1%). Hemoglobin <10 g/dl, serum creatinine at admission >1.5 mg/dl, HbA1c% >10%, and immunosuppression had statistically significant association with the development of multiorgan dysfunction on univariate analysis, but on multivariate analysis, only hemoglobin, HbA1c%, and immunosuppression reached statistical significance. Even with attributable risk of mortality, only hemoglobin, HbA1c%, and immunosuppression reached statistical significance on multivariate analysis. HbA1c% adds to the predictive parameters to recognize at-risk patients to intensify the treatment and avoid complications.
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CASE REPORTSTop

Hepatitis C virus-associated membranoproliferative glomerulonephritis treated with directly acting antiviral therapyp. 462
S Nayak, A Kataria, MK Sharma, A Rastogi, E Gupta, A Singh, SC Tiwari
DOI:10.4103/ijn.IJN_235_17  
Hepatitis C virus (HCV) infection has been shown to affect kidneys with various histopathological pattern on the kidney biopsy. These commonly include a membranoproliferative glomerulonephritis (MPGN) pattern with mixed cryoglobulinemia (CG), thrombotic microangiopathy, membranous nephropathy, and vasculitis affecting medium and small vessels of the kidneys causing polyarteritis nodosa. It has been rarely associated with MPGN without detectable CG. We present one such patient who presented to us with HCV-associated MPGN without detectable CG, who recovered completely with directly acting antiviral therapy without any immunosuppression.
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Systemic lupus erythematosus with linear IgA bullous dermatosis and renal vascular lesions: An extremely rare associationp. 465
R Malipatel, V Gnanapriya, A Manocha, YK Inchara
DOI:10.4103/ijn.IJN_200_17  
We report a rare case of systemic lupus erythematosus presenting initially with cutaneous manifestations of linear IgA bullous dermatosis. Later the patient developed renal abnormalities due to thrombotic microangiopathy and lupus nephritis with inflammatory necrotizing vasculitis. Paucity of immune deposits was observed on Immunofluorescence. This association of SLE with these cutaneous and renal lesions is rarely reported in the literature.
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Xanthogranulomatous pyelonephritis: Intrahepatic and intrathoracic extensionp. 468
U Anandh, N Birajdar, R Kumar, S Babu
DOI:10.4103/ijn.IJN_213_17  
A 32-year-old female presented to us with worsening cough and expectoration, low-grade fever, and malaise for 3 months. She gave a history of pregnancy loss secondary to urinary tract infection (UTI) a year back. At that time, she was told to have an obstructive right renal calculus. She also had a history of recurrent UTI in the past 1 year. She had no other comorbidities. Her clinical evaluation revealed an enlarged right kidney and reduced air entry in the right hemithorax. Radiological investigations revealed a large right kidney invading into the inferior surface of the right lobe of the liver and the right pleural space. A clinical diagnosis of xanthogranulomatous pyelonephritis was made, and she was advised nephrectomy. Intraoperatively, the right kidney was found to invade both the right lobe of the liver and the right pleural cavity through a right diaphragmatic defect. Histopathology of the kidney revealed the presence of foamy histiocytes suggestive of xanthogranulomatous pyelonephritis. Invasive xanthogranulomatous pyelonephritis is known, however, invasion into the extra-abdominal structures has not been reported in the literature. Our case is a rare manifestation of a rare clinical entity – xanthogranulomatous pyelonephritis.
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Crystalline nephropathy in renal transplant: A series of 4 casesp. 472
K Mnif, S Yaich, M Mars, K Kammoun, F Fendri, K Charfeddine, F Jarraya, T Boudawara, J Hachicha
DOI:10.4103/ijn.IJN_76_17  
Crystals are particles of endogenous inorganic or organic composition that can trigger kidney injury when deposited or formed inside the kidney. The most common forms of crystalline nephropathies (CNs) are nephrocalcinosis and oxalate nephropathy. The causes of early allograft dysfunction are changing constantly, and recently calcium oxalate (CaOx) crystal deposition has been added to this list. CaOx deposition in renal allograft is important and probably under-recognized cause of delayed graft function that requires adequate awareness with early intervention to improve the allograft outcome. Here, we describe four cases of irreversible renal graft injury due to CNs.
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Allopurinol-induced drug reactions with eosinophilia and systemic symptoms syndrome with interstitial nephritisp. 477
T Aatif, J Fatihi, H El Annaz, O Qamouss
DOI:10.4103/ijn.IJN_166_17  
Allopurinol-induced drug reactions with eosinophilia and systemic symptoms (DRESS) is a severe illness related to hypersensitivity syndrome characterized by fever, skin rash, lymph node enlargement, hematological abnormalities, especially eosinophilia and atypical lymphocytosis, and single or multiple organ involvement. The syndrome is difficult to diagnose in view of its clinical heterogeneity and long latency period within 8 weeks after start treatment. We report a case of DRESS syndrome in a 64-year-old man, induced by allopurinol treatment for asymptomatic hyperuricemia, started 8 weeks earlier but stopped only 3 days after because of the onset of rash. The diagnosis was retained due to combining of interstitial nephritis with the clinical findings of fever, skin rash, cervical lymphadenopathy, eosinophilia, and reactivation of human herpesviruses specifically HHV-6. The glucocorticoids were started to relieve hypersensitivity. Five days later, the patient became afebrile, and the rash improved significantly. However, interstitial nephritis with renal function impairment progressed to severe azotemia, and even anuria requiring hemodialysis. Allopurinol-induced DRESS syndrome is associated with significant mortality, and care must, therefore, be exercised when given this drug.
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Autosomal dominant polycystic kidney disease: Presence of hypomorphic alleles in PKD1 Genep. 482
S Pandita, D Khullar, R Saxena, IC Verma
DOI:10.4103/ijn.IJN_236_17  
Autosomal dominant polycystic kidney disease is characterized by multiple cysts in both kidneys manifesting in adult life. In general, the disorder is caused by a pathogenic variant in one allele of PKD1 or PKD2 genes, while the other allele is normal. Pathogenic variants in both the alleles are rare and have variable phenotypes, from lethal or perinatal presentation to a mild form in later adulthood, depending on the type of variant. Here, we describe a proband with two variants (p.Thr1773Ile and p.Ala1871Thr in trans) in PKD1 gene, who presented with disease at age 24 years. Both the parents and one brother had a variant in one allele, the other being wild type only and had normal ultrasound findings. Segregation studies suggest that both the variants may act as "hypomorphic" or "incompletely penetrant" alleles and acting together resulted in haploinsufficiency of protein PC1 in renal cells, leading to cystogenesis in the proband. The consequences of the presence of two hypomorphic variants have been poorly documented in literature. We reviewed the few published cases having two hypomorphic variants and the data conform to the conclusions that we reached by study of the family described. It is emphasized that to resolve the significance of suspected hypomorphic variants, segregation studies in the parents and siblings are essential.
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An unusual association of renal cell carcinoma and renal malakoplakia with focal segmental glomerulosclerosis in an elderly patientp. 485
M Vijayan, P Koshy, R Parthasarathy, M Mathew, G Abraham
DOI:10.4103/ijn.IJN_289_17  
The association of malignancy and glomerulonephritis may be missed, especially in elderly patients. Here, we report a case of eosinophilic variant of renal cell carcinoma and renal parenchymal malakoplakia discovered on renal biopsy in a patient with steroid-dependent nephrotic syndrome. The presence of malakoplakia in our biopsy was probably due to systemic steroid therapy for glomerulonephritis, presence of concomitant asymptomatic urinary tract infection, and/or history of diabetes mellitus. The patient had remission of proteinuria following laparoscopic removal of the tumor, indicating probable remission of glomerulonephritis.
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Kidney transplantation from a hepatitis C virus-positive donor to a hepatitis C virus-negative recipient Highly accessed articlep. 488
M Kamalkiran, V Ravikiran, C Shashidhar, K. V. R Prasad, V Yeldandi
DOI:10.4103/ijn.IJN_267_17  
Kidney transplantation from a hepatitis C virus (HCV)-positive donor to an HCV-negative recipient till recently has been a contraindication. In view of the excellent sustained virological response (SVR) rates with directly acting antiviral agents, HCV-positive donors are being considered for the HCV-negative recipients in a few centers. We report the successful transplantation of an HCV-negative recipient transplanted with an HCV-positive donor kidney. Donor was treated with sofosbuvir and ribavirin for 12 weeks. At 10th and 16th weeks of starting treatment, her HCV-RNA PCR was negative. Three weeks later, transplantation was performed with basiliximab induction and triple immunosuppression with tacrolimus, mycophenolate, and prednisolone. The recipient was administered sofosbuvir and ribavirin for 12 weeks. He attained good graft function with a stable creatinine. His serial alanine transaminases were normal on 3rd, 6th, and 12th months, respectively. Six months posttransplant his anti-HCV antibody, and HCV-RNA PCR were negative.
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LETTERS TO EDITORTop

Cystinuria in a 13-Month-Old girl with absence of mutations in the SLC3A1 and SLC7A9 genesp. 490
MD Al-Mendalawi
DOI:10.4103/ijn.IJN_46_18  
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Improving crossmatch techniques and graft outcomesp. 491
L Vincent
DOI:10.4103/ijn.IJN_362_17  
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Estimated glomerular filtration rate using creatinine-based chronic kidney disease epidemiology collaboration equationp. 492
AA Rani, V Viswanathan
DOI:10.4103/ijn.IJN_439_17  
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