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.

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.

Impact of C1q fixing donor-specific antibodies on renal transplant outcome.

Not all anti-HLA donor-specific antibodies (HLA-DSAs) are detrimental to renal allograft. In this context, the C1q complement activating ability of antibodies appears to be an important parameter to distinguish clinically inert versus detrimental DSAs. We evaluated sera of 206 consecutive primary live donor renal transplant recipients before transplant and at post-operative day 7, 30, 90, 180 and at the time of graft dysfunction for quantifying HLA-DSAs using single antigen bead assay on a Luminex platform. Patients positive for these antibodies with an MFI >500 were further screened for C1q fixing nature of DSA. Fourteen of the 18 antibody-positive patients had C1q fixing DSA with MFI value >5000. Only 4 antibody-positive patients did not have C1q fixing DSA. The MFI values of DSA detected by C1q assay were generally higher at least by 25% than those detected by the conventional IgG-SAB assay. Twelve of the 14 patients (85.71%) with C1q+ DSA developed antibody-mediated rejection during the mean follow-up period of 21.43 ± 8.03 months as compared to none of the four C1q-negative DSA (85.71% vs 0%; P = .001). These results suggest deleterious effect of C1q+ DSA vis-à-vis C1q-negative DSA on renal allograft.

Pulmonary infections after renal transplantation: a prospective study from a tropical country.

Pulmonary infection is a leading cause of morbidity and mortality in renal transplant recipients. In a prospective study, we characterized their epidemiology in a tropical country with high infectious disease burden. Adult renal transplant recipients presenting with pulmonary infections from 2015 to 2017 were evaluated using a specific diagnostic algorithm. 102 pulmonary infections occurred in 88 patients. 32.3% infections presented in the first year, 31.4% between 1 and 5, and 36.3% beyond 5 years after transplantation. Microbiological diagnosis was established in 69.6%, and 102 microorganisms were identified. Bacterial infection (29.4%) was most common followed by tuberculosis (23.5%), fungal (20.6%), Pneumocystis jiroveci (10.8%), viral (8.8%), and nocardial (6.9%) infections. Tuberculosis(TB) and bacterial infections presented throughout the post-transplant period, while Pneumocystis (72.7%), cytomegalovirus (87.5%) and nocardia (85.7%) predominantly presented after >12 months. Fungal infections had a bimodal presentation, between 2 and 6 months (33.3%) and after 12 months (66.7%). Four patients had multi-drug resistant(MDR) TB. In 16.7% cases, plain radiograph was normal and infection was diagnosed by a computed tomography imaging. Mortality due to pulmonary infections was 22.7%. On multivariate Cox regression analysis, use of ATG (HR-2.39, 95% CI: 1.20-4.78, P = 0.013), fungal infection (HR-2.14, 95% CI: 1.19-3.84, P = 0.011) and need for mechanical ventilation (9.68, 95% CI: 1.34-69.82, P = 0.024) were significant predictors of mortality in our patients. To conclude, community-acquired and endemic pulmonary infections predominate with no specific timeline and opportunistic infections usually present late. Nocardiosis and MDR-TB are emerging challenges.

Outcomes of symptomatic coronavirus disease 19 in maintenance hemodialysis patient in India.

BACKGROUND: Maintenance hemodialysis (MHD) patients face disadvantages with higher risk of acquiring SARS-CoV-2 infection, atypical manifestations, and associated multiple comorbidities. We describe patients' outcomes with symptomatic COVID-19 on MHD in a large cohort of patients from India. METHODS: Data were collected prospectively from hemodialysis units in 11 public and private hospitals between March 15, 2020, and July 31, 2020. The survival determinants were analyzed using stepwise backward elimination cox-regression analysis. RESULTS: Of the 263 total patients (mean age 51.76 ± 13.63 years and males 173) on MHD with symptomatic COVID-19, 35 (13.3%) died. Those who died were older (p = 0.01), had higher frequency of diabetic kidney disease (p = 0.001), comorbidities (p = 0.04), and severe COVID-19 (p = 0.001). Mortality was higher among patients on twice-weekly MHD than thrice-weekly (p = 0.001) and dialysis through central venous catheter (CVC) as compared to arteriovenous fistula (p = 0.001). On multivariate analysis, CVC use (HR 2.53, 95% CI 1.26-5.07, p = 0.009), disease severity (HR = 3.54, 95% CI 1.52-8.26, p = 0.003), and noninvasive ventilatory support (HR 0.59, 95% CI 0.25-0.99, p = 0.049) had significant effect on mortality. CONCLUSION: The adjusted mortality risk of COVID-19 in MHD patients is high in patients associated with severe COVID-19 and patients having CVC as vascular access.

Evaluation of the Graft Kidney in the Early Postoperative Period: Performance of Contrast-Enhanced Ultrasound and Additional Ultrasound Parameters.

OBJECTIVES: To evaluate the various quantitative parameters of Doppler ultrasound, contrast-enhanced ultrasound (CEUS), and shear wave elastography (SWE) of graft kidneys in the early postoperative period and to explore their utility in the diagnosis of parenchymal causes of graft dysfunction. METHODS: In this ethically approved study, consecutive patients who underwent renal transplantation from March 2017 to August 2018 were recruited, and those with urologic or vascular complications and those who denied consent were excluded. All patients underwent ultrasound with Doppler, SWE, CEUS (using sulfur hexafluoride), and renal scintigraphic examinations 3 to 10 days after transplantation. A composite reference standard was used, including the clinical course, renal function test results, urine output, and histopathologic results for graft dysfunction. Cortical SWE values, quantitative CEUS parameters (generated from a time-intensity curve), and their ratios were analyzed to identify graft dysfunction and differentiate acute tubular necrosis (ATN) from acute rejection (AR). RESULTS: Of the 105 patients included, 19 developed graft dysfunction (18.1%; 12 ATN, 5 AR, and 2 drug toxicity) in the early postoperative period. The peak systolic velocity in the interpolar artery showed a significant difference between control and graft dysfunction groups (P < .001) as well as between ATN and AR (P = .019). Resistive indices and SWE did not show significant differences. Ratios of the time to peak showed a significant difference between control and graft dysfunction groups (P < .05). The rise time and fall time of the large subcapsular region of interest and the rise time ratio were significantly different between ATN and AR (P = .03). CONCLUSIONS: Contrast-enhanced ultrasound can be used to diagnose parenchymal causes of early graft dysfunction with reasonable diagnostic accuracy.

Clinical relevance of major histocompatibility complex class I chain-related molecule A (MICA) antibodies in live donor renal transplantation - Indian Experience.

Antibody-mediated rejections (AMR) in the absence of circulating anti-HLA-DSA have highlighted the role of non-HLA antibodies, particularly those directed against endothelial cells. Of these, MICA (major histocompatibility complex class I chain-related molecule A) antibodies are the most notable and important because of their potential in promoting graft rejections. Limited studies have focused on the impact of MICA donor-specific antibodies (DSA) on graft outcome as compared to those that are not donor-specific (NDSA). We evaluated pre- and post-transplant sera at POD 7, 30, 90, 180 and the time of biopsy from 206 consecutive primary live donor renal transplant recipients for anti-MICA and anti-HLA antibodies using single antigen bead assay on a Luminex platform. Recipients who developed MICA antibodies and their donors were phenotyped for MICA alleles. For the purpose of antibody analysis, patients were categorized into three major groups: biopsy-proven AMR, acute cellular rejection (ACR) and those with no rejection episodes (NRE). During the mean follow-up period of 17.37 ± 6.88 months, 16 of the 206 recipients developed AMR, while ACR was observed in only 13 cases. A quarter (25%) of the AMR cases had anti-MICA antibodies as compared to 7.7% of those experiencing ACR and 6.2% of the NRE group. Allelic typing revealed that all MICA Ab +ve AMR cases were due to the presence of donor-specific antibodies. MICA-DSA even in the absence of HLA-DSA was significantly associated with AMR but not with ACR when compared with the NRE group (P = <.01).

Diabetes, Hypertension and Kidney Disease Combination "DHKD Syndrome" is common in India.

Objectives: The study was designed to find out frequency of (i) Diabetes mellitus (DM) as a cause Chronic Kidney Disease (CKD), (ii) Association between diabetic-CKD (diabetic patients who subsequently developed CKD as complication), hypertension (HT) and obesity. Further assessment was made to (iii) Identify percentage of diabetics attending medical and nephrology OPD had prior testing for proteinuria and or creatinine. Methods: After ethical consideration this prospective observational study was conducted on consecutive 6175 patients who gave consent to participate in two major referral hospitals one in Delhi and other in Bhubaneswar (BBSR). Primary hypertension was defined as blood pressure of ≥140/90 mmHg detected before onset of DM or detected together in the absence of CKD (elevated serum creatinine S Cr ≥1.7 mg/dL and or proteinuria > 0.3g/24H). Upper limit of serum creatinine was kept at 1.7 mg for this study. Mean value of three estimations on different days was recorded. Detail clinical history of DM and HT was taken. Body Mass Index (BMI), ocular fundi examination, urine analysis, serum creatinine, lipid profile, blood glucose, HbA1C tests were conducted in all patients. They were regularly followed up in renal clinic at about 2 month interval for repeat investigations. Blood pressure in nondiabetic-CKD patients was recorded for comparison. Further, consecutive diabetic patients attending general medicine OPD for first time were examined, their previous investigations were carefully scrutinized and recorded. Urine for albuminuria and serum creatinine were tested every month over a period of one year. Results: In Delhi diabetic-CKD was observed in 68.4% and the same was 56.2% in BBSR giving a combined figure of 62.3 percent. On close analysis of past record primary hypertension was observed in 75.4% who subsequently developed diabetes and CKD. Frequency of association between diabetic-CKD and HT were 88.2% and 69.3% in two cities respectively, combined frequency being 78.7 percent. Association of diabetic-CKD and obesity was 55.1 % and 55.9% in two cities respectively with combined frequency of 55.5 percent. In contrast obesity in non-diabetic-CKD patients in Delhi and BBSR was found in 43.1% and 18.5% respectively, combined frequency being 30.8%. Fifty four percent of diabetic patients who attended medical OPD for the first time were found to have proteinuria and elevated serum creatinine. However, they were not earlier tested for those parameters. Hence, they were unaware of CKD. Conclusion: Diabetes was found to be a bigger cause (62.3%) of CKD than what has been reported thus far in India. At presentation association of diabetic-CKD with HT was recorded higher (78.7%) in India. Hence use of the syndrome "DHKD", (complex of diabetes, hypertension and kidney disease) is justifiable. Our study shows 54.4% of diabetic patients attending medicine OPD were uninvestigated by either physician or GP for CKD because urine albumin and serum creatinine tests were lacking. Thus, progression to CKD in many patients went unnoticed. Syndromic diagnosis of "DHKD" therefore in our view is important to create general awareness for early detection and effective treatment of diabetic nephropathy.

BK polyomavirus infection after renal transplantation: Surveillance in a resource-challenged setting.

BACKGROUND: There is a paucity of data available about BK polyomavirus (BKPyV) infection after renal transplantation (RTX) in resource-limited countries with a predominantly living-donor, ABO-compatible RTX program. We aimed to assess BKPyV infection in such patients in a public hospital in India. METHODS: We prospectively evaluated plasma BKPyV replication in 62 patients at 1, 3, 6, 9, and 12 months after RTX. Sustained significant BK viremia (SSBKV) was defined as significant viremia (≥10 000 copies/mL) detected ≥2 times, and BKPyV-associated nephropathy (BKVAN) as histologic changes of BKVAN with BK viremia with/without graft dysfunction. RESULTS: All patients underwent RTX without requiring desensitization. Incidence of BK viremia was: 17.7%, 41.9%, 16.1%, 25.8%, and 17.7% at 1, 3, 6, 9, and 12 months, respectively. Of 62 patients, 64.5% had BKPyV viremia during the study, 32.2% had significant viremia, all except one detected in the first 6 months. Nine (14.5%) patients had SSBKV. There was no biopsy-proven BKVAN. At the end of 1 year, mean serum creatinine was higher and graft dysfunction was significantly more common in patients with SSBKV compared to those without SSBKV. CONCLUSION: Transient BK viremia is common in low/intermediate immunologic risk RTX recipients in India, with a peak occurring at 3-6 months. Most clear their viremia by 12 months. Graft dysfunction seems to be more frequent in patients with SSBKV, although BKVAN is uncommon on biopsy in these patients.

Comparative analysis of Luminex-based donor-specific antibody mean fluorescence intensity values with complement-dependent cytotoxicity & flow crossmatch results in live donor renal transplantation.

BACKGROUND & OBJECTIVES: Antibodies specific to donor human leucocyte antigen (HLA) play a critical role in graft rejection and graft loss. In recent years, techniques for their detection have evolved significantly providing an ever-increasing degree of sensitivity and specificity, from the conventional cell-based assays to the advanced solid-phase system based on the Luminex platform. Consensus is still evolving on the routine employment of all these methods, either stand alone or in combination. The objective of this study was to explore the near-accurate mean fluorescence intensity (MFI) cut-off values detected on Luminex platform predicting the strength of cell-based crossmatch results. METHODS: Serum samples from 116 primary renal transplant recipients awaiting transplantation were tested for the presence of antidonor antibodies by the complement-dependent cytotoxicity (CDC) and flow crossmatch (FCXM) methods with their corresponding donors as well as for HLA-donor-specific antibodies (DSA) detection using a sensitive single antigen bead (SAB) assay. RESULTS: None of the patients having HLA Class I DSA with MFI values <1000 showed positivity for T-cell FCXM or CDC crossmatch, while in the group having MFI values between 1000 and 3000, 54 per cent showed positivity for the FCXM but none by the CDC method. However, in the group having MFI values >3000, 95 per cent of cases were positive for FCXM. Further, those groups with MFI values between 3000 and 5000, only 36 per cent were positive for CDC crossmatch, while 90 per cent showed positivity in the group with MFI >7000. INTERPRETATION & CONCLUSIONS: A cut-off MFI value of 3000 for Luminex SAB-based assay was found to significantly correlate with the FCXM positivity while a MFI value of 7000 and above predicted a positive CDC crossmatch. MFI cut-off value obtained as a surrogate marker for CDC and FCXM tests will help in resolving the limitations of different cell-based techniques.

Association of impaired baroreflex sensitivity and increased arterial stiffness in peritoneal dialysis patients.

BACKGROUND: Peritoneal dialysis patients have high cardiovascular morbidity and mortality. The underlying mechanism of cardiovascular dysfunction remains unclear. Large arterial stiffness in chronic kidney disease (CKD) patients leads to increase in pulse wave velocity (PWV) and decrease in baroreflex sensitivity (BRS). Impairment in baroreflex function could be attributed to the alteration in mechanical properties of large vessels due to arterial remodeling observed in these patients. The present study was designed to study the association of BRS and PWV in peritoneal dialysis (PD) patients. METHODS: 42 CKD patients (21--without dialysis and 21--on PD) and 25 healthy controls were recruited in this study. BRS was determined by spontaneous sequence method. Short-term heart rate variability (HRV) and blood pressure variability (BPV) were assessed using power spectrum analysis of RR intervals and systolic blood pressure by time domain and frequency domain analysis. Arterial stiffness indices were assessed by carotid-femoral PWV using Sphygmocor Vx device (AtCor Medical, Australia). RESULTS: CKD patients had significantly high PWV and low BRS as compared to healthy controls. PWV had a significant negative correlation with BRS in CKD patients (Spearman r = -0.7049, P < 0.0001; BRS-Systolic BP). On subgroup analysis, PWV was higher with lower BRS in CKD patients on peritoneal dialysis (CKD-PD) as compared to those not on dialysis (CKD-ND). Negative relationship between PWV and BRS was found in both the groups. In addition, BRS was found to have a positive correlation with HRV in CKD patients as well as both the subgroups. CONCLUSION: Reduction in BRS is strongly associated with increase in PWV in PD patients. Large arterial stiffness probably explains this simultaneous impairment in baroreflex functioning and increase in pulse wave velocity observed in these patients. CKD patients are characterized by poor hemodynamic profile (low BRS, high PWV, and low HRV), and peritoneal dialysis patients had further worsened profile as compared to non-dialysis group.

Clinical and histopathologic profile of patients with primary IgA nephropathy seen in a tertiary hospital in India.

BACKGROUND: IgA nephropathy (IgAN) is known to have an aggressive course in Asians. There is a paucity of data regarding the Oxford classification pattern of Indian patients with IgAN. This study aims to characterize the clinical and histopathologic profile of these patients. METHODS: All patients diagnosed to have primary IgAN by kidney biopsy in the nephrology department from July 2009 to July 2014 were included in this study. All kidney biopsies were reviewed and the MEST score was assigned as per the Oxford classification. The clinical features and Oxford classification score of patients were characterized. RESULTS: Nephrotic range proteinuria (NRP) (65/103, 63.1%) with or without edema was the commonest presentation. 67.0% patients had eGFR ≥ 60 mL/min and 16.5% patients had eGFR < 30 mL/min. Of the 103 patients, 80 (77.7%) had M1, 10 (9.7%) had E1, 45 (43.7%) had S1 and 41 (39.8%) had T1/T2 lesions by the Oxford criteria and 11 (10.7%) patients had crescents. 62 patients had eGFR ≥ 30 mL/min and follow up for at least 6 months (median -17.7 (6-65.1) months) of whom 52(83.9%) had received ACEi/ARBs and 38 (61.3%) had received immunosuppression. 11/62 (17.7%) patients developed renal worsening in this period of which 7 (11.3%) developed end stage kidney disease (ESKD). CONCLUSION: Indian patients with primary IgA nephropathy have a unique profile. They commonly present with nephrotic range proteinuria. A significant proportion of these patients have normal renal function despite heavy proteinuria. Mesangial proliferative lesions are predominant with a paucity of endocapillary proliferation and crescents compared to other Asian populations. Immunosuppressive use is more common in Indian patients.

Risk factors of suicide among patients admitted with suicide attempt in Tata main hospital, Jamshedpur.

BACKGROUND: More than one lakh lives are lost every year due to suicide in India. In the last three decades (from 1975 to 2005), the suicide rate has increased by 43%. Jamshedpur is an Industrial town, which is rapidly growing and having population with mixed cultural background. Recently, there has been increasing trend in a number of suicide attempt across various age groups; there are around 300 cases of suicide attempt admitted to Tata Main Hospital each year. OBJECTIVE: To study the risk factors associated with suicide attempts. METHODS: The study was carried out in the Tata Main Hospital, Jamshedpur. Over a period of 6 months, we gathered data of 101 suicide attempters referred from medical, surgical departments and casualties and taken up for the study. Data were collected on specific pro forma was prepared to collect various others risk factors. RESULTS: More number of female patients compared to male, younger age, lower-middle income group, urban background, school educated, and unemployed were more represented in this study. In 70% of patients, psychiatric disorder was found, but few among them had prior treatment. Increased family conflicts, marital problems, financial difficulties, and perceived humiliations are some of the risk factors. CONCLUSION: The early identification and treatment of vulnerable populations with risk factors for suicide across the lifespan will help in planning and implementing strategies for prevention.

Monoclonal gammopathy of renal significance with light-chain deposition disease diagnosed postrenal transplant: a diagnostic and therapeutic challenge.

Patients with light-chain deposition disease (LCDD) frequently do not meet criteria for myeloma. In such cases, despite low tumor burden, the circulating monoclonal immunoglobulins cause renal damage, are responsible for post-transplant recurrence, and are rightly categorized as monoclonal gammopathy of renal significance (MGRS) requiring chemotherapy. A 65-year male with uncharacterized nodular glomerulopathy presented with proteinuria 3 years postrenal transplant. His allograft biopsies were diagnostic of light-chain deposition disease (likely recurrent), and in the absence of myeloma, he was labeled as MGRS. Based on the limited literature available, he was treated with bortezomib which resulted in normalization of serum-free light-chain ratios and resolution of proteinuria. He, however, later succumbed to complications of chemotherapy. This case highlights the diagnostic difficulties in LCDD, the importance of an accurate pretransplant diagnosis, and treatment of the malignant clone, in the absence of which post-transplant management of recurrence is challenging with poor outcomes.

Characterization of the novel HLA-B*15:05:01:02 allele by sequence-based typing.

HLA-B*15:05:01:02 differs from HLA-B*15:05:01:01 by one nucleotide change in intron 2 at position 517 (C > A).

One nucleotide substitution in the 3'UTR generated the novel allele HLA-B*40:01:02:47 in a North Indian individual.

HLA-B*40:01:02:47 differs from HLA-B*40:01:02:01 by one nucleotide change in the 3'UTR at position 2739 (A>T).