Visual, rapid, and cost-effective BK virus detection system for renal transplanted patients using gold nanoparticle coupled loop-mediated isothermal amplification (nanoLAMP).

A substantial percentage of kidney transplant recipients show transplant failure due to BK virus-induced nephropathy. This can be clinically controlled by the rapid and timely detection of BK virus infection in immune-compromised patients. We report a rapid (two hours from sample collection, processing, and detection), cost-effective (< 2$), highly sensitive and BKV-specific nanoLAMP (loop-mediated isothermal amplification) diagnostic methodology using novel primers and gold nanoparticles complex-based visual detection. The standardized nanoLAMP showed an analytical sensitivity of 25 copies/µl and did not cross-react with closely related JC and SV40 viruses. This nanoLAMP showed diagnostic sensitivity and specificity as 91% and 96%, respectively, taking 50 BK virus-negative (confirmed by qPCR from the plasma of healthy donors) and 57 positive BKV patient samples (confirmed by clinical parameters and qPCR assay). This simple two-step, low-cost, and quick (1-2 h/test) detection would be advantageous over the currently used diagnostic methodology. It may change the paradigm for polyomavirus infection-based failure of renal transplant.

Clinical Profile of Nonproteinuric Kidney Disease in Type 2 Diabetic Patients in India.

Background: Diabetic kidney disease (DKD) is the commonest cause of end-stage renal disease (ESRD) across the world. Development of microalbuminuria is the earliest marker of DKD and predicts progressive decline in estimated glomerular filtration rate (eGFR). However, recent evidence has suggested that a significant proportion of type 2 diabetic patients have chronic kidney disease (CKD) without proteinuria. Methods: In this single-center, prospective observational study, 400 consecutive type 2 diabetic patients with either overt proteinuria (>500 mg/day) and/or renal dysfunction eGFR <60 ml/min/1.73 m2) were recruited. Baseline demographic and clinical data were recorded. eGFR and proteinuria were recorded at 6 months and 1 year. Patients with proteinuric (proteinuria >0.5 g/day) and nonproteinuric phenotypes were compared for progression of renal dysfunction in terms of doubling of serum creatinine and need for dialysis. Results: In our study cohort, 106 (26.5%) were nonproteinuric. Both the groups were similar in terms of gender, duration of diabetes, comorbidities, body mass index (BMI), blood pressure control, and glycemic control. The nonproteinuric group was older (56.5 ± 2.1 vs. 54.7 ± 11.6 years, P = 0.012), had lesser prevalence of diabetic retinopathy (49 [46.2%] vs. 218 [74.1%], P < 0.001), higher hemoglobin levels (11.3 ± 1.7 vs. 10.5 ± 2.0 g/dl, P < 0.001), and higher cholesterol levels (169.3 ± 43.3 vs 157.1 ± 58.1 mg/dl, P = 0.025). The nonproteinuric phenotype had higher eGFR at baseline, 6 months, and 1 year. However, doubling of serum creatinine (10 [9.4%] vs. 48 [16.3%]) and progression to ESRD (5 [4.7%] vs. 19 [6.5%], P = 0.159) were not different between the two phenotypes. Conclusion: Nonproteinuric DKD is common. Patients with nonproteinuric DKD tend to be older with a slower decline in eGFR.

Effect of vinpocetine alone and in combination with enalapril in experimental model of diabetic cardiomyopathy in rats: possible involvement of PDE-1/TGF-ß/ Smad 2/3 signalling pathways.

OBJECTIVE: Diabetic cardiomyopathy (DC) is one of the severe secondary complications of diabetes mellitus in humans. Vinpocetine is an alkaloid having pleiotropic pharmacological effects. The present study is designed to investigate the effect of vinpocetine in DC in rats. METHODS: Rats were fed a high-fat diet for nine weeks along with single dose of streptozotocin after the second week to induce DC. The haemodynamic evaluation was performed to assess the functional status of rats using the Biopac system. Cardiac echocardiography, biochemical, oxidative stress parameters and inflammatory cytokine level were analysed in addition to haematoxylin-eosin and Masson's trichome staining to study histological changes, cardiomyocyte diameter and fibrosis, respectively. Phosphodiesterase-1 (PDE-1), transforming growth factor-ß (TGF-ß) and p-Smad 2/3 expression in cardiac tissues were quantified using western blot/RT-PCR. KEY FINDING: Vinpocetine treatment and its combination with enalapril decreased the glucose levels compared to diabetic rats. Vinpocetine improved the echocardiographic parameters and cardiac functional status of rats. Vinpocetine decreased the cardiac biochemical parameters, oxidative stress, inflammatory cytokine levels, cardiomyocyte diameter and fibrosis in rats. Interestingly, expressions of PDE-1, TGF-ß and p-Smad 2/3 were ameliorated by vinpocetine alone and in combination with enalapril. CONCLUSIONS: Vinpocetine is a well-known inhibitor of PDE-1 and the protective effect of vinpocetine in DC is exerted by inhibition of PDE-1 and subsequent inhibition of the expression of TGF-ß/Smad 2/3.

Factors affecting quality of daytime and nighttime sleep among dialysis patients: A single center experience.

BACKGROUND: Hemodialysis is the most common treatment modality for patients with chronic kidney disease (CKD). Excessive daytime sleepiness and poor nighttime sleep is a common problem among these patients. Patients on maintenance hemodialysis (MHD) are regularly exposed to impaired fluid balance, which may cause overhydration of varying degree. However, the role of hydration status in sleep quality has not been explored in Indian setting. Hence, this study was undertaken to assess the factors affecting sleep quality among patients on MHD in a tertiary care hospital. MATERIAL AND METHODS: Patients (N = 55) were enrolled if they aged above18 years, on MHD for at least 3 months, and gave consent. The daytime sleep quality was assessed using Epworth Sleepiness Scale (ESS) and Insomnia Severity Index (ISI). The data were analyzed using SPSS version 20 and STATA software. RESULTS: The mean age of the patients was 40.4 ± 14.7 years. The prevalence rate of predialysis fluid overload was 85.4%. The median ESS score was 7 and ISI score was 3 indicating normal daytime sleep and not significant insomnia. Multivariate regression with variables adjustment showed that interdialytic weight gain (P = 0.33), tingling sensation (P = 0.36) and numbness (P = 0.35) were significant predictive factors for quality of sleep. CONCLUSION: The major factors affecting sleep quality were numbness, tingling sensation, and interdialytic weight gain. Fluid overload did not play any role in sleep quality. Another study may be carried out on assessment of pattern, duration, quality of sleep in multiple dialysis sessions, and effect of optimizing fluid status on the sleep parameters.

Utility and patient acceptance of telemedicine in nephrology.

PURPOSE: There is an increasing burden of kidney diseases worldwide and access to specialist care is limited. Telemedicine, has been relatively less used in developing countries like India. The current study aims to assess the feasibility and acceptance of telenephrology services at our institute, a public hospital. METHODS: A total of 150 patients were selected by stratified random sampling from the list of attendees who had undergone both in-person outpatient consultation and telenephrology consultation. Patient's attitude towards, and knowledge and acceptance of telenephrology services were evaluated. RESULTS: The average age of the study cohort was 42.52 ± 15.1 years. More than one-third (39.3%) of our patients belonged to the lower middle socioeconomic class. The median distance traveled to reach our outpatient clinic was 113.5 km (3-2249 km). Patients reported lost workdays in 54.7% cases. The majority (95%) of patients managed to consult through teleservices successfully. Ninety percent of the patients gave a satisfaction score of 4 (out of 5) or above for their tele-consultation experience. The most important perceived benefit of teleconsultation was the reduced risk of infection (40.6%) followed by economic benefits (32%). The major disadvantage (36%) was the absence of physical examination. A combination of physical and telenephrology services was the option preferred by 84% of the patients. CONCLUSION: In developing countries like India, with the majority of the population residing outside major cities and with limited medical access, telenephrology has a huge potential to provide quality nephrology care to the remotest parts of the country.

The International IgA Nephropathy Network Prediction Tool Underestimates Disease Progression in Indian Patients.

Introduction: International IgA nephropathy (IgAN) network (IIgANN) prediction tool was developed to predict risk of progression in IgAN. We attempted to externally validate this tool in an Indian cohort because the original study did not include Indian patients. Methods: Adult patients with primary IgAN were stratified to low, intermediate, higher, and highest risk groups, as per the original model. Primary outcome was reduction in estimated glomerular filtration rate (eGFR) by >50% or kidney failure. Both models were evaluated using discrimination: concordance statistics (C-statistics), time-dependent receiver operating characteristic (ROC) curves, R2d, Kaplan-Meier survival curves between risk groups and calibration plots. Reclassification with net reclassification improvement and integrated discrimination improvement (IDI) was used to compare the 2 models with and without race. Results: A total of 316 patients with median follow-up of 2.8 years had 87 primary outcome events. Both models with and without race showed reasonable discrimination (C-statistics 0.845 for both models, R2d 49.9% and 44.7%, respectively, and well-separated survival curves) but underestimated risk of progression across all risk groups. The calibration slopes were 1.234 (95% CI: 0.973-1.494) and 1.211 (95% CI: 0.954-1.468), respectively. Both models demonstrated poor calibration for predicting risk at 2.8 and 5 years. There was limited improvement in risk reclassification risk at 5 and 2.8 years when comparing model with and without race. Conclusion: IIgANN prediction tool showed reasonable discrimination of risk in Indian patients but underestimated the trajectory of disease progression across all risk groups.

Metabolic acidosis in the initial 6 months after renal transplantation: A prospective study.

BACKGROUND: There is limited information about the incidence of metabolic acidosis (MA) after renal transplantation. This single centre prospective study aimed to delineate the incidence and risk factors of MA in the first 6 months after renal transplantation (RTX). DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: Patients who underwent RTX between November 2018 and July 2020 were monitored with weekly measurement of serum bicarbonate level for 6 months and those who were diagnosed with MA were evaluated further to characterize the type of MA. RESULTS: One hundred and twenty-five patients were included in the study, 89 (71.2%) of whom developed MA. Seventy-two patients developed MA in the first month, 11 during the 2-3 months and 6 between 4 and 6 months after transplantation. Of the 89 patients, 55(61.8%) had type 1 renal tubular acidosis (T1RTA), 27 (30.3%) had type 2 RTA (T2RTA) and 7 (7.9%) type 4 RTA (T4RTA). Two patient who had T1RTA, subsequently developed high anion gap MA following severe graft rejection. On stepwise multivariate regression analysis, serum creatinine at time of diagnosis of MA [OR (95% CI): 12.02 (1.79 to 80.59), p = .01] and high tacrolimus C0 levels [OR (95% CI): 2.43 (1.0 to 5.90), p = .049], were independent risk factors for MA. CONCLUSION: There is a high incidence of MA in the initial 6 months post-transplant with serum creatinine and high tacrolimus C0 levels being independent risk factors.

Characterizing predictors of non-diabetic kidney disease (NDKD) in diabetic patients.

BACKGROUND: Diabetic kidney disease (DKD) is the chief cause of renal involvement in diabetic patients. It is primarily a clinical diagnosis. Non-diabetic kidney disease (NDKD) may be missed if they are not biopsied. In this study, we describe the spectrum of NDKD and evaluate the predictors considered for planning a biopsy in diabetic patients with kidney disease. METHODS: In a retrospective cohort study, diabetic patients who underwent kidney biopsy at our centre between May 2006 and July 2019 were evaluated for NDKD. RESULTS: 321 diabetic patients who underwent kidney biopsy were analyzed. Mean age was 49.3 ± 12.4 years and 71% were males. 75.8% patients had hypertension and 25.2% had diabetic retinopathy. Based on the kidney biopsy, patients were classified as DKD-127 (39.6%), NDKD-179(55.8%) and combined DKD + NDKD-15(4.7%). Overall, the most commonly diagnosed pathology was membranous nephropathy-MN (17%), followed by IgA nephropathy (16.0%) and focal segmental glomerulosclerosis-FSGS (14.9%). In patients with DKD + NDKD, IgA nephropathy (53.3%) was predominant. 165 (51.4%) patients had a diagnosis potentially amenable to a specific therapy. On multivariate analysis, female gender [OR 2.07 (1.08-3.97), p = 0.02], absence of diabetic retinopathy [OR 7.47 (3.71-15), p < 0.001] absence of hypertension [OR 3.17 (1.56-6.45), p = 0.001] and duration of diabetes ≤ 24 months [OR 3.67(1.97-6.84), p < 0.001], were independent predictors for NDKD while the absence of nephrotic range proteinuria [OR 1.73 (0.98-3.05), p 0.05] showed a trend towards significance. CONCLUSION: Astute use of kidney biopsy can detect potentially treatable NDKD in a large number of diabetic patients with glomerular diseases being the predominant diagnosis. A combination of risk factors needs to be considered to guide the need for kidney biopsy in diabetic patients.

An experimental study to evaluate the effect of low-intensity intradialytic exercises on serum urea, creatinine, and fatigue of chronic kidney disease patients undergoing hemodialysis.

In chronic kidney disease (CKD) toxins accumulate in the muscles and cause fatigue, mental impairment, and muscle dysfunction (cramps). Exercise results in the opening of capillaries thereby increasing blood flow and allowing greater movement of urea and creatinine from the tissues to the vascular compartment and subsequent removal through dialysis. An experimental study of 64 CKD patients (32 each in experimental and control group), six low-intensity intra-dialytic exercises (IDE) were implemented for experimental group using video demonstration at 90 min after initiation of hemodialysis (HD) repeated thrice at an interval of 10 mins. Pre- and post-HD serum urea, creatinine, and fatigue levels were assessed at baseline, two, four and six weeks. Fatigue was measured using FACIT scale. Significant difference was found between the control and experimental group in serum urea, creatinine and fatigue levels (P = 0.007, P = 0.001, P = 0.001) at six weeks post HD. The experimental group showed a significant decrease in creatinine levels from baseline to six weeks (P = 0.04). Ninety-seven percent of patients were compliant to low-intensity IDE with patients feeling better and comfortable along with decrease in felt fatigue levels. No significant association was found between duration of illness, duration of maintenance HD and comorbidities and serum urea, serum creatinine, and fatigue levels (P = 0.5, P = 0.21, P = 0.78). The present study shows low-intensity IDE when performed regularly, was effective in decreasing serum urea, creatinine, and fatigue levels of CKD patients undergoing HD with vital signs remaining within the normal range. No overt complications were reported; hence, the exercises were safe.

Low-dose Rituximab therapy in resistant idiopathic membranous nephropathy: single-center experience.

BACKGROUND: Persistent significant proteinuria has been associated with increased risk of progression to end-stage kidney disease in patients with idiopathic membranous nephropathy (IMN). Rituximab (RTX) therapy has given encouraging results in IMN, but most of the studies have used a higher dose, which is limited by the high cost as well as a potential increased risk of infections. Our study aimed to assess the efficacy and safety of low-dose RTX in patients with immunosuppression-resistant IMN. METHODS: A total of 21 patients with treatment-resistant IMN treated with RTX from 2015 to 2016 at our center were included in the study. They received two doses of RTX (500 mg each) infusion 7 days apart. CD19 count was performed after 4 weeks. A single dose of RTX was repeated after 4-6 weeks if CD19 count was not depleted. RESULTS: The mean standard deviation age of patients was 33.3 ± 12.3 years and 33.3% were females. Mean proteinuria before RTX therapy was 6.2 ± 2.2 g/day, serum creatinine was 0.9 ± 0.3 mg/dL and estimated glomerular filtration rate (eGFR) was 95.8 ± 26.9 mL/min/1.73 m2. All the patients were non-responders to prior immunosuppressive treatment. Twenty (95.2%) patients achieved targeted CD19 depletion with two doses of RTX. One patient required one additional RTX dose due to inadequate B-cell suppression. A total of 13 (61.9%) patients achieved remission with RTX therapy: 4 (19.0%) complete and 9 (42.9%) partial remission. Patients who did not respond to RTX had a significantly lower baseline eGFR compared with those who achieved remission (P = 0.022). One patient developed respiratory tract infection following RTX during the follow-up, which responded to a course of oral antibiotics. During median follow-up of 13.1 (10-23.9) months, four (19%) patients had deterioration in renal function and one patient relapsed after achieving partial remission. Renal survival was significantly better in patients who responded to RTX therapy as compared with those who did not achieve remission (P = 0.0037). CONCLUSION: Low-dose RTX therapy is effective and safe in immunosuppression-resistant IMN.

Intravenous immunoglobulin therapy for dengue capillary leak syndrome in a renal allograft recipient.

A 45-year-old man presented 4 months after ABOi renal transplantation with febrile illness and bicytopenia necessitating cessation of mycophenolate mofetil. Dengue non-structural protein 1 antigen (NS1 Ag) test was positive. Lowest total leucocyte count was 3.1×109/L and platelet count was 14×109/L. As fever subsided, patient became tachypneic with abdominal distention and hypotension. Ultrasonographic evaluation revealed ascites, gall bladder wall oedema and bilateral pleural effusion consistent with dengue capillary leak syndrome. He developed massive ascites with abrupt weight gain of 4 kg within 24 hours and worsening renal dysfunction. Patient was deteriorating rapidly in spite of adequate supportive care and we gave a trial of intravenous immunoglobulin (0.5 g/kg/day) for 5 days. Patient improved from day 2, and by day 3, he became haemodynamically stable and recovered completely. Patient was stable at discharge and is on regular follow-up.

Colovesical fistula: a rare complication after renal transplantation.

Colovesical fistula per se is a rare condition and most commonly occurs secondary to diverticular disease in normal patients. Colovesical fistula in the setting of post-renal transplantation is even rarer and very few cases have been reported in literature. Patients with autosomal-dominant polycystic kidney disease (ADPKD) are predisposed to diverticulosis and hence are at a higher risk for fistula formation. Herein, we report a case of colovesical fistula in a renal allograft recipient with ADPKD in the absence of diverticulosis. The patient was successfully operated and is stable with no complications at 1-year follow-up.

Asymptomatic pontine and extra-pontine lesions in a patient with end-stage renal disease.

Osmotic demyelination syndrome leading to central pontine/extra-pontine myelinolysis (CPM/EPM) occurs mainly in patients with history of alcohol abuse, malnourishment, following liver transplantation and less commonly, in association with other systemic diseases. Asymptomatic CPM/EPM is rare. Patients with end-stage renal disease (ESRD) who develop CPM/EPM are usually symptomatic with florid neurologic manifestations. Herein, we present a patient with ESRD on maintenance hemodialysis who was incidentally detected to have pontine and extra-pontine lesions suggestive of myelinolysis without any neurologic signs or symptoms.