Desidustat in Anemia due to Dialysis-Dependent Chronic Kidney Disease: A Phase 3 Study (DREAM-D).

BACKGROUND: A phase 3 study to assess the efficacy and safety of the desidustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, against the epoetin alfa for the treatment of anemia in patients with chronic kidney disease (CKD) with dialysis dependency. METHODS: DREAM-D was a phase 3, multicenter, open-label, randomized, active-controlled clinical study conducted across 38 centers in India. A total of 392 patients with clinical diagnosis of anemia due to CKD with dialysis need (Erythrocyte Stimulating Agent [ESA] naïve or prior ESA users) and with baseline hemoglobin levels of 8.0-11.0 g/dL (inclusive) were randomized in a 1:1 ratio to receive either desidustat oral tablets (thrice a week) or epoetin alfa subcutaneous injection for 24 weeks to maintain a hemoglobin level of 10-12 g/dL. The primary endpoint was to assess the change in the hemoglobin level between the desidustat and the epoetin alfa groups from the baseline to evaluation period week 16-24. The key secondary efficacy endpoint was the number of patients with hemoglobin response. RESULTS: The least square mean (standard error) change in hemoglobin from the baseline to week 16-24 was 0.95 (0.09) g/dL in the desidustat group and 0.80 (0.09) g/dL in the epoetin alfa group (difference: 0.14 [0.14] g/dL; 95% confidence interval: -0.1304, 0.4202), which met the prespecified noninferiority margin. The number of hemoglobin responders was significantly higher in the desidustat group (106 [59.22%]) when compared to the epoetin alfa group (89 [48.37%]) (p = 0.0382). The safety profile of the desidustat oral tablet was comparable with the epoetin alfa injection. There were no new risks or no increased risks seen with the use of desidustat compared to epoetin alfa. CONCLUSION: In this study, desidustat was found to be noninferior to epoetin in the treatment of anemia in CKD patients on dialysis and it was well-tolerated. Clinical Trial Registry Identifier: CTRI/2019/12/022312 (India).

A retrospective multi-center experience of renal transplants from India during COVID-19 pandemic.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) pandemic led to a sudden drop in renal transplant numbers across India in the initial months of 2020. Although the transplant numbers increased with easing of lockdown, the outcome of these transplants remains unknown. METHODS: This was a retrospective, observational, multi-center study done across eight different transplant centers in India. All the transplants done from January 30, 2020 to December 31, 2020 were included. The primary outcomes studied were patient and death censored graft survival as well as incidence of COVID-19 infection and its outcomes. RESULTS: During the study period a total of 297 kidney transplants were done. After a median follow up of 265 days the patient and death censored graft survival was 95.3% and 97.6%, respectively. Forty-one patients (13.8%) developed COVID-19 post-transplant. Majority (58.5%) were asymptomatic to mildly symptomatic and the case fatality ratio was 14.6%. On multivariable logistic regression analysis older age was associated with higher likelihood of COVID-19 infection (odds ratio 1.038; CI 1.002-1.077). CONCLUSIONS: Patient and graft outcome of kidney transplants done during the COVID-19 pandemic in India was acceptable. The incidence of COVID-19 was 13.8% with a high case fatality ratio.

Indian College of Physicians (ICP) Position Statement on Pharmacovigilance.

Pharmacovigilance is the art and science of detection, understanding and prevention of adverse drug reactions and not merely a critical analysis of prescriptions and errors. This field starts with reporting by clinicians of a suspected adverse drug reaction (ADR) to the pharmacologist followed by joint causality analysis and ends at the application of new information by a clinician for benefit of patients. There are a number of ways, which can be utilised for reporting adverse effects using pen and paper format to software applications for smart phones. Varied types of activities spreading from systematic reviews to the mechanistic evaluation of ADR can be performed under the umbrella of pharmacovigilance. It is of utmost importance for clinicians to understand how to identify, communicate and understand adverse effects of drugs with an aim to prevent harm to patients.

Indian College of Physicians Position Statement: Addictive Disorders Among Persons with Diabetes Mellitus.

OBJECTIVES: Migraine, a common primary headache disorder which can be severely disabling, associated with poor health-related quality of life (HRQoL) amongst affected patients. The present study was performed to provide adequate clinical data on migraine and the management practices in India. MATERIAL AND METHODS: A cross-sectional study was designed to assess disease burden, HRQoL, symptom profile, management trends and comorbidities associated with migraine patients across ten centres in India. This study assessed HRQoL using Migraine Specific Quality of life (MSQ) and Migraine Disability Assessment Scores (MIDAS) questionnaire. Categorical variables were summarized as frequency, and percentage and continuous variables as mean and standard deviation respectively. RESULTS: A total of 705 patients were enrolled with a mean age of 35.2 years. Hypertension (7.0%) was the highest co-morbid illness associated with migraine. A higher MSQ score was observed in females as compared to males (39.3±12.4 and 37.4±11.6) while MIDAS showed a comparable score (27.7±47.6 and 27.2±35.4). Majority of migraine patients were unemployed (61.6%) and in profession, females had poor HRQoL than males by MIDAS and MSQ. Majority of patients had pulsating, bilateral attacks for the duration of 4h to 72 h. Paracetamol (47.1%) and propranolol (50.9%) was most commonly prescribed drugs for acute attack and prophylaxis, respectively. CONCLUSION: The quality of life was superior in males as compared to females amongst migraine patients in India. Hypertension was the commonest comorbidity associated with migraine. KEY MESSAGES: Migraine is associated with substantial disability with higher prevalence in females and older people (age >40 years). NSAIDs and propanol was widely prescribed drug in acute attacks and prophylaxis of migraine respectively. Cardiovascular diseases, diabetes mellitus and anxiety were common comorbidities associated with migraine.

Community-acquired acute kidney injury in India: data from ISN-acute kidney injury registry.

Background: Acute kidney injury (AKI), particularly community-acquired AKI (CA-AKI), is a major health concern globally. The International Society of Nephrology's "0 by 25" initiative to reduce preventable deaths from AKI to zero by 2025 is not achievable in low and middle income countries, such as India, possibly due to a lack of data and measures to tackle this urgent public health issue. In India, CA-AKI predisposes younger patients to hospitalization, morbidity, and mortality. This is the first multicenter, prospective, cohort study investigating CA-AKI and its consequences in India. Methods: This study included data from patients with CA-AKI (>12 years of age) housed in the Indian Society of Nephrology-AKI registry, involving 9 participating tertiary care centers in India, for the period between November 2016 and October 2019. The etiological spectrum and renal and patient outcomes of CA-AKI at the index visit and at 1-month and 3-month follow-ups were analyzed. The impact of socioeconomic status (SES) on outcomes was also analyzed. Findings: Data from 3711 patients (mean [±SD] age 44.7 ± 16.5 years; 66.6% male) were analyzed. The most common comorbidities included hypertension (21.1%) and diabetes (19.1%). AKI occurred in medical, surgical, and obstetrical settings in 86.7%, 7.3%, and 6%, respectively. The most common causes of AKI were associated with sepsis (34.7%) and tropical fever (9.8%). Mortality at the index admission was 10.8%. Complete recovery (CR), partial recovery (PR), and dialysis dependency among survivors at the time of discharge were 22.1%, 57.7%, and 9.4%, respectively. Overall, at 3 months of follow-up, mortality rate, CR, PR, and dialysis dependency rates were 11.4%, 72.2%, 7.2%, and 1%, respectively. Multivariate analysis revealed that age >65 years, alcoholism, anuria, hypotension at presentation, thrombocytopenia, vasopressor use, transaminitis, and low SES were associated with mortality at the index admission. Interpretation: Sepsis and tropical fever were the most common causes of CA-AKI. Presentation of CA-AKI to tertiary care units was associated with high mortality, and a significant number of patients progressed to CKD. Individuals with a low SES had increased risk of mortality and require immediate attention and intervention. Funding: This study was funded by the Indian Society of Nephrology.

South Asian Transplant Infectious Disease Guidelines for Solid Organ Transplant Candidates, Recipients, and Donors.

These guidelines discuss the epidemiology, screening, diagnosis, posttransplant prophylaxis, monitoring, and management of endemic infections in solid organ transplant (SOT) candidates, recipients, and donors in South Asia. The guidelines also provide recommendations for SOT recipients traveling to this region. These guidelines are based on literature review and expert opinion by transplant physicians, surgeons, and infectious diseases specialists, mostly from South Asian countries (India, Pakistan, Bangladesh, Nepal, and Sri Lanka) as well as transplant experts from other countries. These guidelines cover relevant endemic bacterial infections (tuberculosis, leptospirosis, melioidosis, typhoid, scrub typhus), viral infections (hepatitis A, B, C, D, and E; rabies; and the arboviruses including dengue, chikungunya, Zika, Japanese encephalitis), endemic fungal infections (mucormycosis, histoplasmosis, talaromycosis, sporotrichosis), and endemic parasitic infections (malaria, leishmaniasis, toxoplasmosis, cryptosporidiosis, strongyloidiasis, and filariasis) as well as travelers' diarrhea and vaccination for SOT candidates and recipients including travelers visiting this region. These guidelines are intended to be an overview of each topic; more detailed reviews are being published as a special supplement in the Indian Journal of Transplantation .

Are we overconcerned about secondary hyperparathyroidism and underestimating the more common secondary hypoparathyroidism in our dialysis patients?

OBJECTIVES: The aim of the study was to determine the prevalence of hyper and hypo-parathyroid state in prevalent dialysis patients. The second part of the study was to look for the prevalence of vascular calcification (abdominal aortic) and factors predicting calcification in these patients. METHODS: All adult patients, who were more than 1 month on dialysis, were included in the study. A total of 68 patients, of which 75% were on hemodialysis and 25% on peritoneal dialysis, were finally studied. Patients' parathyroid status was defined as per target recommendation of KDOQI--hypoparathyroid with iPTH < or = 150 pg/ml and hyperparathyroid with iPTH > 300 pg/ml. Vascular calcification was determined by X ray of lateral lumbar spine to look for abdominal aortic calcification (AAC). The AAC was scored as validated. The prevalence of hyper- and hypoparathyroidism in dialysis patients was determined as percentage of total dialysis patients. The prevalence of AAC and factors predicting it was analyzed by 'univariate' and 'multiple logistic regression analyses. RESULTS: The mean age of patients was 50.04 +/- 14.15 years, 58.82% were males and 42.64% were diabetics. Mean duration of dialysis was 22.36 +/- 19.17 months. Hyperparathyroidism was seen in only 27.94% of all dialysis patients, while hypoparathyroidism was in 45.58%. Abdominal aortic calcification was seen in 79.41% of overall patients and 13.23% had significant calcification (score 7-24). On univariate analysis, age (0.000) and iPTH (0.03) were the only variables predicting AAC and on logistic regression analysis, age was the only independent predictor of abdominal aortic calcification (p = 0.002, OR 1.11, CI 1.038-1.186). CONCLUSION: Hypoparathyroidism is more common (46%) in our dialysis patients as compared to hyperparathyroidism (28%). There is high prevalence of vascular (abdominal aortic) calcification (80%) in our dialysis patients.

Cardiorenal disease management in type 2 diabetes: An expert consensus.

BACKGROUND AND AIM: The interplay between cardiovascular disease (CVD), chronic kidney disease (CKD) and type 2 diabetes (T2D) is well established. We aim at providing an evidence-based expert opinion regarding the prevention and treatment of both heart failure (HF) and renal complications in people with T2D. METHOD: ology: The consensus recommendations were developed by subject experts in endocrinology, cardiology, and nephrology. The criteria for consensus were set to statements with ≥80% of agreement among clinicians specialized in endocrinology, cardiology, and nephrology. Key expert opinions were formulated based on scientific evidence and clinical judgment. RESULTS: Assessing the risk factors of CVD or CKD in people with diabetes and taking measures to prevent HF or kidney disease are essential. Known CVD or CKD among people with diabetes confers a very high risk for recurrent CVD. Metformin plus lifestyle modification should be the first-line therapy (unless contraindicated) for the management of T2D. Glucagon-like peptide 1 (GLP-1) agonists can be preferred in people with atherosclerotic cardiovascular disease (ASCVD) or with high-risk indicators, along with sodium-glucose cotransporter-2 inhibitors (SGLT2i), whereas SGLT2i are the first choice in HF and CKD. The GLP-1 agonists can be used in people with CKD if SGLT2i are not tolerated. CONCLUSION: Current evidence suggests SGLT2i as preferred agents among people with T2D and HF, and for those with T2D and ASCVD. SGLT2i and GLP-1RA also lower CV outcomes in those with diabetes and ASCVD, and the treatment choice should depend on the patient profile.

Survival of elderly/dialysis patients--a single center study from India.

OBJECTIVE: In the absence of national registry and uniformity of treatment, survival of patients on dialysis in our country has been variedly reported. There are no published data on survival of elderly patients (>65 years) on dialysis. Because of several social, economical and practical reasons (mentioned below), not many elderly chronic kidney disease patients opt for dialysis. It is worth while to look into the data of survival of elderly CKD (chronic kidney disease) patients on dialysis to justify the treatment. All CKD patients who continued dialysis for more than 1 month at our center from 1st November 2006 to 31st August 2009 were included in the analysis. Patients who moved to their native place after initiation of dialysis, underwent transplant, discontinued dialysis for personal reasons, or died in the first month were excluded. The survival analysis (Kaplan-Meier) and the demographics were calculated for the elderly group and compared with the young ones (Independent sample T-test). 86 adult patients were included in the retrospective survival analysis, out of which 18 were elderly (21%). Mean age of elderly patients on dialysis was 72.3 +/- 7 years. 77.7 % were males and 77.7 % were diabetics. Median survival of these patients was 25.6 months (SE 10, and 95% CI 5.9 - 45.3) while the younger ones had a median survival of 79.6 months (SE 7.9, 95% CI 64 - 95.3). 24 months survival calculated from KM data set was 41.1% in the elderly whereas it was 96.9% in the young age group. It is conclude that Median survival of elderly dialysis patients is more than 2 years and 2 year survival is more than 40%. Elderly CKD patients, hence, should be encouraged for renal replacement therapy rather than discouraging them with poor survival.

A Rare Case of APRT Deficiency with End-stage Renal Failure and Successful Renal Transplant.

Renal calculus disease is a common cause of renal injury. However, crystal nephropathy (uric acid, oxalate, and dihydroxyadenine) can present as chronic kidney disease without any evidence of renal stones. If left undiagnosed, there is a potential chance of recurrence in the allograft leading to graft failure after transplantation. Pretransplant identification and management can avoid such complications. Here, we describe a case of APRT deficiency leading to crystal nephropathy and end-stage renal failure in a patient who underwent a successful kidney transplant.

Continuous Ambulatory Peritoneal Dialysis Peritonitis Guidelines - Consensus Statement of Peritoneal Dialysis Society of India - 2020.

Continuous ambulatory peritoneal dialysis (CAPD) related peritonitis is a major cause of technique failure, morbidity, and mortality in patients on CAPD. Its prevention and management is key to success of CAPD program. Due to variability in practice, microbiological trends and sensitivity towards antibiotics, there is a need for customized guidelines for management of CAPD related peritonitis (CAPDRP) in India. With this need, Peritoneal Dialysis Society of India (PDSI) organized a structured meeting to discuss various aspects of management of CAPDRP and formulated a consensus agreement which will help in management of patients with CAPDRP.

Alport's Syndrome: A Rare Clinical Presentation with Crescents.

Alport's syndrome (hereditary nephritis) is a familial disorder, which usually affects young males with clinical presentation of hematuric and glomerular disease. We report a rare case of Alport's syndrome in a 16-year-old male with typical extrarenal manifestations and renal biopsy findings with crescents.

Intradialytic Hypertension Increases Non-access Related Hospitalization and Mortality in Maintenance Hemodialysis Patients.

BACKGROUND AND AIMS: Intradialytic hypertension, in patients on maintenance hemodialysis, is associated with increased morbidity and mortality. As there is no data available from India, this study was aimed to determine the prevalence and outcome of intradialytic hypertension (IDH) in a tertiary care dialysis centre in India. METHODS: This was a prospective analytical study of 120 patients on hemodialysis. At screening phase, all patients were subjected to fluid optimization and adjustment in the antihypertensive medicines for appropriate control of blood pressure (BP). BP measurements during hemodialysis were recorded. The prevalence of IDH was noted. IDH was defined as increase in systolic BP of >10 mmHg from pre to post hemodialysis or after 2nd hour of dialysis when significant ultrafiltration had occurred, on 3 consecutive sessions. Factors associated with IDH were evaluated and compared with cohort without IDH. The outcome of these patients in terms of morbidity and mortality over a follow-up period of 12 months were recorded. RESULTS: The prevalence of IDH was 21.9%. The baseline demographic parameters of patients in both the groups (with and without IDH) including age, sex, dialysis access, duration of dialysis, and comorbidities were similar. Laboratory parameters were similar except serum potassium and serum phosphorus, which were lower in patients with IDH. Out of all the variables studied, only low serum phosphorus was associated independently with IDH. During follow-up, at 6 months, 19/71 (26%) non-IDH and 12/20 (60%) IDH patients (P = 0.006) and at 12 month, 30/71 (42%) non-IDH patients and 12/20 (60%) IDH patients required admission (P = 0.05). Mortality at 6 months was similar, 5/71 (7%) in non-IDH and 4/20 (20%) in IDH (P = 0.10) patients, but was higher at 12 months, 11/71 (15.5%) in non-IDH and 8/20 (40%) in IDH (P = 0.028). CONCLUSION: Incidence of intradialytic hypertension is high (21.9%) with increased morbidity in terms of hospitalization and increased mortality over a period of one year.

Peritoneal Dialysis Patients During COVID 19 Pandemic.

COVID pandemic poses challenges to peritoneal dialysis patients, caretaker, and service provider to the PD patients as well. The chronic peritoneal dialysis (PD) patients are trained to do the PD procedure at home, therefore can avoid in-center hospital visit unlike patients on hemodialysis. Thus, PD patients can avoid undue exposure to the novel coronavirus. The PD can be offered in COVID induced AKI patients, even in remote places where hemodialysis cannot be offered. The paper is aimed to provide guidelines about the safe use of PD and treatment of complications during the COVID pandemic.

The Adverse Effect of COVID Pandemic on the Care of Patients With Kidney Diseases in India.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has affected the care of patients with noncommunicable diseases, including those suffering from kidney-related ailments. Many parts of the world, including India, adopted lockdown to curb community transmission of disease. The lockdown affected transportation, access to health care facilities, and availability of medicines and consumables as well as outpatient and inpatient services. We aimed to analyze the effect of lockdown imposed due to the COVID-19 pandemic on the care of patients with kidney diseases in India. METHODS: We surveyed 19 major hospitals (8 in the public and 11 in the private sector) to determine the effect of lockdown on the care of patients with kidney disease, including those on dialysis after the first 3 weeks of lockdown. RESULTS: The total number of dialysis patients in these centers came down from 2517 to 2404. Approximately 710 (28.2%) patients missed 1 or more dialysis sessions, 69 (2.74%) required emergency dialysis sessions, 104 (4.13%) stopped reporting for dialysis, and 9 (0.36%) were confirmed to have died. Outpatient attendance in the surveyed hospital came down by 92.3%, and inpatient service reduced by 61%. Tele-consultation was started but was accessed by only a small number of patients. CONCLUSION: Lack of preparedness before lockdown resulted in an interruption in health care services and posed an immediate adverse effect on the outcome of dialysis patients and patients with kidney disease in India. The long-term impact on the health of patients with less severe forms of kidney disease remains unknown.

The variability in ultrafiltration achieved with icodextrin, possibly explained.

BACKGROUND: A recent study by Jeloka et al. (Perit Dial Int 2006; 26:336-40) highlighted the high variability in maximum ultrafiltered volume (UF(max)) and the corresponding dwell time (t(max)) obtained using 7.5% icodextrin solution. We aimed to pinpoint the possible sources of this phenomenon by simulating the icodextrin ultrafiltration (UF) profiles according to the three-pore model of peritoneal transport. METHOD: The individual UF time courses observed in the study by Jeloka et al. (n = 29) were first characterized by linear and quadratic regression. We were then able to identify four main patterns. These were then adapted to UF profiles generated by the three-pore model by systematically altering the values of some model parameters, namely, the mass transfer area coefficient (MTAC or PS) for icodextrin/glucose, the peritoneal UF coefficient (LpS), the plasma colloid osmotic pressure gradient (DeltaPi), and the macromolecular clearance out of the peritoneal cavity (Cl(LF)). RESULTS: Modifications in the PS values caused only marginal variations in UF(max) and t(max), while more significant changes were produced by altering LpS and Cl(LF). However, far more evident was the importance of changes in DeltaPi. In fact, lowering DeltaPi to 14 mmHg caused a steady increase in UF with 10 - 14 hour dwells. On the contrary, the UF profiles became nearly "flat" when DeltaPi was increased to 30 mmHg. The parallel shifts induced by altering icodextrin metabolite concentrations did not markedly influence UF(max) or t(max). CONCLUSION: The UF pattern in icodextrin dwells seem to be mainly determined by the plasma colloid osmotic pressure, while only moderate changes can be seen with alterations in LpS and Cl(LF). The result is not completely unexpected considering that icodextrin acts by inducing a strong colloid osmotic gradient. A number of clinical studies would be needed, however, in order to prove this hypothesis.

Calciphylaxis in a renal transplant recipient with normal graft function: A case report and review of literature.

Calciphylaxis, also known as calcific uremic arteriolopathy, is a rare, life-threatening complication of end-stage renal disease. However, it may also occur in patients without renal failure, the nonuremic calciphylaxis. Most patients present with painful skin ulcers. Delayed diagnosis can lead to sepsis-related morbidity and mortality. Aberrations in calcium, phosphate, and parathyroid hormone physiology are common and biopsy is diagnostic. Early diagnosis and correction of vascular and metabolic aberrations may assist in healing as may the use of sodium thiosulfate and hyperbaric oxygen therapy. We report on successful treatment of a case of calciphylaxis in a renal transplant recipient with normal allograft function.

Icodextrin produces higher ultrafiltration in diabetic than in non-diabetic patients on continuous cyclic peritoneal dialysis.

A preliminary report from our unit previously suggested that diabetic patients on continuous cyclic peritoneal dialysis (CCPD) have higher ultrafiltration (UF) with icodextrin than non-diabetic patients. To confirm this observation, we did a retrospective analysis of our patients (17 diabetic and 23 non-diabetic) who were on stable CCPD prescription using a long-day dwell with icodextrin. We collected daily UF data from these patients' records for 30 days. The two groups showed no significant difference with respect to age, gender, hemoglobin, serum albumin, peritoneal dialysis and icodextrin vintage, peritoneal membrane characteristics, CCPD prescription, and peritoneal and residual renal clearance. The overnight net UF achieved with the cycler with standard glucose dialysate was similar in the two groups (850+/-379 in diabetic vs 713+/-484 ml/day in non-diabetic, P=0.34). However, UF with icodextrin during the day dwell (14.8+/-0.8 h) was significantly higher in diabetics than non-diabetics (348+/-198 vs 137+/-311 ml/day, P=0.02). Our results show that icodextrin produces significantly higher UF in long-day dwell in diabetic ESRD patients on CCPD than in non-diabetic patients. The reason for this difference is not clear.

Comparison of antibody titers using conventional tube technique versus column agglutination technique in ABO blood group incompatible renal transplant.

INTRODUCTION: Measurement of alloantibody titer to a red cell antigen (ABO titers) is an integral part of management of ABO incompatible kidney transplants (ABOiKT). MATERIAL AND METHODS: There are different methods of titer estimation. Alloantibody detection by tube titration and Gel agglutination columns are accepted methodologies. It is essential to find the difference in titers between the two methods so as to set the 'cut-off' titer accordingly, depending upon the method used. RESULTS: We did a prospective observational study to compare and correlate the ABO titers using these two different techniques - conventional tube technique (CTT) and the newer column agglutination technique (CAT). A total of 67 samples were processed in parallel for anti-A/B antibodies by both tube dilution and column agglutination methods. The mean titer by conventional tube method was 38.5 + 96.6 and by the column agglutination test was 96.4 + 225. The samples correlated well with Spearman rho correlation coefficient of 0.94 (P = 0.01). CONCLUSION: The column agglutination method for anti A/B titer estimation in an ABO incompatible kidney transplant is more sensitive, with the column agglutination results being approximately two and half fold higher (one more dilution) than that of tube method.