Clinicopathologic Spectrum and Outcomes of Infections Diagnosed on Graft Biopsies and Nephrectomy in Live Renal Allograft Recipients: An Institutional Experience.

OBJECTIVES: Modern immunosuppressive regimens have reduced rejection episodes in renal allograft recipients but have increased the risk of opportunistic infections. Infections are considered to be the second leading cause of death after cardiovascular complications in renal allograft recipients. Data on opportunistic infections affecting the allograft itself are scarce. The present study describes the spectrum of renal opportunistic infections and their outcomes diagnosed on renal allograft biopsies and nephrectomy specimens. MATERIALS AND METHODS: Our retrospective observational study was conducted from December 2011 to December 2021. We analyzed infectious episodes diagnosed on renal allograft biopsies or graft nephrectomy specimens. We obtained clinical, epidemiological, and laboratory details for analyses from hospital records. RESULTS: BK virus nephropathy was the most common opportunistic infection affecting the allograft, accounting for 47% of cases, followed by bacterial graft pyelonephritis (25%). Mucormycosis was the most common fungal infection. The diagnosis of infection from day of transplant ranged from 14 days to 39 months. Follow-up periods ranged from 1 to 10 years. Mortality was highest among patients with opportunistic fungal infection (62%), followed by viral infections, and graft failure rate was highest in patients with graft pyelonephritis (50%). Among patients with BK polyomavirus nephropathy, 45% had stable graft function compared with just 33% of patients with bacterial graft pyelonephritis. CONCLUSIONS: BK polyoma virus infection was the most common infection affecting the renal allograft in our study. Although fungal infections caused the highest mortality among our patients, bacterial graft pyelonephritis was responsible for maximum graft failure. Correctly identifying infections on histology is important so that graft and patient life can be prolonged.

Are Differences in Living Kidney Donation Rates a Sex or a Gender Disparity?

Sex-disaggregated data reveal significant disparities in living kidney donation, with more female than male living kidney donors in most countries and proportions over 60% in some countries. We summarize the present state of knowledge with respect to the potential drivers of this disparity and argue that it is primarily driven by gender-related factors. First, we present the differences between sex and gender and then proceed to summarize the potential medical reasons that have been proposed to explain why males are less likely to be living kidney donors than females, such as the higher prevalence of kidney failure in males. We then present counterarguments as to why biological sex differences are not enough to explain lower living kidney donation among males, such as a higher prevalence of chronic kidney disease among females, which could affect donation rates. We argue that gender differences likely provide a better explanation as to why there are more women than men living kidney donors and explore the role of economic and social factors, as well as gender roles and expectations, in affecting living kidney donation among both men and women. We conclude with the need for a gender analysis to explain this complex psychosocial phenomenon in living kidney donation.

Practice of dialysis access interventional nephrology procedures in the Asia-Pacific region: Getting lay of the land.

AIM: This cross-sectional survey aimed to determine the prevalence of Interventional Nephrology (IN) practice amongst nephrologists in the Asia-Pacific Region (APR), specifically related to dialysis access (DA). METHODS: The Association of VA and intervenTionAl Renal physicians (AVATAR) Foundation from India conducted a multinational online survey amongst nephrologists from the Asia-Pacific to determine the practice of IN in the planning, creation, and management of dialysis access. The treatment modalities, manpower and equipment availability, monthly cost of treatment, specifics of dialysis access interventions, and challenges in the training and practice of IN by nephrologists were included in the survey. RESULTS: Twenty-one countries from the APR participated in the survey. Nephrologists from 18 (85.7%) countries reported performing at least one of the basic dialysis access-related IN procedures, primarily the placement of non-tunnelled central catheters (n-TCC; 71.5%). Only 10 countries (47.6%) reported having an average of <4% of nephrologists performing any of the advanced IN access procedures, the most common being the placement of a peritoneal dialysis (PD) catheter (20%). Lack of formal training (57.14%), time (42.8%), incentive (38%), institutional support (38%), medico-legal protection (28.6%), and prohibitive cost (23.8%) were the main challenges to practice IN. The primary obstacles to implementing the IN training were a lack of funding and skilled personnel. CONCLUSION: The practice of dialysis access-related IN in APR is inadequate, mostly due to a lack of training, backup support, and economic constraints, whereas training in access-related IN is constrained by a lack of a skilled workforce and finances.

The Power and Promise of Angiotensin Receptor Neprilysin Inhibitor (ARNI) in Heart Failure Management: National Consensus Statement.

;Heart failure (HF) is a huge global public health task due to morbidity, mortality, disturbed quality of life, and major economic burden. It is an area of active research and newer treatment strategies are evolving. Recently angiotensin receptor-neprilysin inhibitor (ARNI), a class of drugs (the first agent in this class, Sacubitril-Valsartan), reduces cardiovascular mortality and morbidity in chronic HF patients with reduced left ventricular ejection fraction (LVEF). Positive therapeutic effects have led to a decrease in cardiovascular mortality and HF hospitalizations (HFH), with a favorable safety profile, and have been documented in several clinical studies with an unquestionable survival benefit with ARNI, Sacubitril-Valsartan. This consensus statement of the Indian group of experts in cardiology, nephrology, and diabetes provides a comprehensive review of the power and promise of ARNI in HF management and an evidence-based appraisal of the use of ARNI as an essential treatment strategy for HF patients in clinical practice. Consensus in this review favors an early utility of Sacubitril-Valsartan in patients with HF with reduced EF (HFrEF), regardless of the previous therapy being given. A lower rate of hospitalizations for HF with Sacubitril-Valsartan in HF patients with preserved EF who are phenotypically heterogeneous suggests possible benefits of ARNI in patients having 40-50% of LVEF, frequent subtle systolic dysfunction, and higher hospitalization risk.

Anti-T-Lymphocyte Immunoglobulin (Grafalon) as an Induction Agent for Renal Transplantation: A Real-World, Retrospective, Single-Center Experience.

OBJECTIVES: Polyclonal antithymocyte globulins are widely used in the induction regimens of solid-organ transplant recipients; however, their doses and outcomes remain to be standardized in Indian patients. We report our clinical experience from the real-world use of Grafalon (an anti-T-lymphocyte globulin; ATG-Fresenius) as an induction agentin renal transplant recipients from India. MATERIALS AND METHODS: In this retrospective, single- center, observational study, we analyzed the medical records of 177 consecutive, kidney-only transplant recipients who received induction therapy with Grafalon from September 2016 to March 2018 at our center. Incidences of biopsy-proven acute rejection and graft dysfunction, immunosuppression protocol, Grafalon dosage, 18-month post-transplant graft and patient survival, treatment-related adverse events, and infective complications were reported. RESULTS: Mean age of patients was 41.46 years (range, 14-68 years), (85% were males). The average dose of Grafalon was 5.81 ± 1.95 mg/kg (range, 2.41 to 10.07 mg/kg). Graft dysfunction (ie, at least 20% increase in serum creatinine from baseline) was observed in 26 patients (14%): 11 patients (6.2%) had biopsy-proven acute rejections, 11 patients (6.2%) had acute tubular necrosis, and 4 patients (2.2%) had calcineurin inhibitor toxicity. Seven deaths were recorded: 2 each from fungal pneumonia, bacterial pneumonia, and acute coronary syndrome and 1 with urinary tract infection with septicemia. Death-censored graft survival was 100% at 12 months and 98% at 18-month follow-up; overall patient survival was 96%. Infective complications occurred in 40 patients (22.5%), with the most common being urinary tract infection in 32 patients (18%). No malignancies were reported. CONCLUSIONS: Use of a potent induction therapy like anti-T-lymphocyte globulin (Grafalon) is often restricted by the risk of side effects and lack of local clinical evidence supporting its role in long-term graft survival. Real-world evidence support the safe and effective use of anti-T-lymphocyte globulin as an induction agent in renal transplant recipients with an individualized dosing approach.

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.

Comparison of short-term outcomes with and without induction therapy in low-risk renal transplant recipients.

With low rates of rejection with current immunosuppression consisting of steroids, mycophenolic acid and tacrolimus, the question arises whether induction offers any additional benefit in low-risk renal transplant recipients. This study evaluated outcomes with and without induction in low-risk renal transplant recipients. A prospective observational study in which 100 low-risk renal transplant recipients were included and divided into two groups - one that received induction (IND) and another that did not (NO IND). They were followed for 1.5 years. Three endpoints were compared - efficacy of induction, patient and graft survival, and adverse effects. Incidence of rejection in early posttransplant period did not differ (4% NO IND vs. 6% IND; P = 0.171). Rejection as cause of late graft dysfunction was seen in 16% in IND vs. 20% NO IND; (P = 0.603). No difference in serum creatinine at end of 1.5 years was seen. Graft survival was also similar. Relapsing and recurrent urinary tract infections (46% IND vs. 16% NO IND; P = 0.09), hospitalization requiring infections (76%IND vs. 64% NO IND; P = 0.119 NS) were more common in IND. Cytomegalovirus infection affected only IND (6% vs. none; P = 0.07). Patient survival at 1.5 years was comparable (94% IND vs. 96% NO IND; P = 0.646). The study showed comparable results between IND and NO IND with however an increased incidence of infections and hospitalizations in the IND group. The use of induction may be avoided in low-risk renal transplant recipients.

Evaluation of Factors Influencing Outcomes in Pauci-Immune Crescentic Glomerulonephritis: Single Centre Experience of 51 Cases.

INTRODUCTION: Pauci-immune crescentic glomerulonephritis (PICGN) is rare form of glomerulonephritis that frequently presents as rapidly progressive renal failure. Several prior studies have evaluated role of various factors influencing outcomes in patients with PICGN. The histopathological classification proposed by Berden a decade earlier described difference in the outcomes of patients in the focal, crescentic, mixed and sclerotic category with best prognosis for focal and worst for sclerotic group. The newly proposed renal risk score of Brix takes into account both the histopathological parameters (% of normal glomeruli, tubular atrophy and interstitial fibrosis) and clinical parameter (eGFR) which influences outcome. METHODS: Retrospective study was performed between 2014 to 2018. Biochemical parameters and ANCA details were recorded and renal histopathology slides were reviewed and classified according to Berden's histopathologic classes. All the cases were further characterized into three groups based on renal risk score (Brix et al). Univariate, multivariate analysis for risk factors predicting ESRD and Kaplan Meier Survival Analysis were done. RESULTS: In the present study, we found eGFR (P 0.024), % of normal glomeruli (P 0.023) and IFTA (P 0.001) as important factors influencing renal outcome in patients with PICGN. More than 60% patients achieved complete remission with low renal risk score as compared to patients with high renal risk score in which 80% patients developed ESRD or death at follow up. We also found significant difference in survival among various renal risk categories (Log-Rank P = 0.001) as compared to Berden's international histological classification (Log-Rank P = 0.037) on Kaplan -Meier survival analysis. CONCLUSION: PICGN is a significant cause of mortality and morbidity. Renal histological factors such as % normal glomeruli at time of biopsy, degree of IFTA and renal risk score play an important role in assessing prognosis in these patients.

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.

Pregnancy-associated osteoporosis: a UK case series and literature review.

Mini Abstract: Pregnancy-associated osteoporosis (PAO) is a rare syndrome affecting women during late pregnancy and the early postpartum period. We set out to review the clinical features of ten cases of PAO from a single UK centre. Patients had attended the Royal National Hospital for Rheumatic Diseases, Bath (RNHRD) between January 2000 and June 2016. The principal criterion for inclusion was the occurrence of low trauma fractures either during pregnancy or the immediate post-partum period. Data were obtained from retrospective review of medical notes. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry (Hologic ®Discovery system) at the lumbar spine and hip. Data pertaining to the pregnancy, as well as type and duration of treatment received, were reviewed. All ten cases presented with vertebral fractures. In four patients, no risk factors for fracture other than pregnancy or breastfeeding could be identified. Four patients were found to have vitamin D insufficiency at the time of diagnosis, and a further two patients had received treatment with low molecular weight heparin (LMWH). In one case, further investigation led to a diagnosis of osteogenesis imperfecta (OI) confirmed on genetic testing. In terms of treatment, eight out of the ten patients in this series received a bisphosphonate, most commonly risedronate due to its relatively short skeletal retention time. Clinicians should be aware of PAO, a rare but recognised complication of pregnancy. The condition should be especially considered in women presenting with new onset back pain in pregnancy or the postpartum period.

BK Virus nephropathy in living donor renal allograft recipients: An observational study from a large transplant center in India.

BK virus is a polyoma virus which remains in latent phase in the urinary tract, particularly in the renal tubular epithelial cells. In immunosuppressed patients, it is activated and manifests as tubule-interstitial nephritis causing renal allograft dysfunction. A total of 402 patients who underwent renal allograft biopsy from 2013 to 2016 were included in this study; six patients were diagnosed to have BK virus nephropathy. Histopathology showed ground glass intra-nuclear inclusions accompanied by acute tubular injury, interstitial inflammation, and varying degree of interstitial fibrosis and tubular atrophy. Patients were managed with reduction in the overall immunosuppression. Only one patient progressed to graft failure on follow-up. The overall prevalence of polyoma virus at our center is 1.49%.

Hypoferremic State in Overweight and Obese Children.

Children with high body mass index (BMI) are at risk of iron deficiency. In present study, 71 children with overweight or obesity were screened for iron deficiency. Mean BMI, ferritin and plasma soluble transferrin receptor (sTrfR) levels were 26.1 kg/m2, 41.9 µg/L and 0.375 mg/L, respectively. Twenty (28%) children had anemia, and 44 (62%) had an underlying hypoferraemic state.

Is there an increased risk of metabolic syndrome among childhood acute lymphoblastic leukemia survivors? A developing country experience.

Data on metabolic syndrome (MS) in survivors of childhood acute lymphoblastic leukemia (ALL) from developing countries are lacking. The purpose of this single-center, uncontrolled, observational study was to assess the frequency of MS in our survivors. The survivors of ALL ≤15 years at diagnosis, who had completed therapy ≥2 years earlier, were enrolled. Anthropometric measurements (weight, height, waist circumference), biochemistry (glucose, insulin, triglycerides, high-density lipoprotein [HDL], thyroid function tests, C-reactive protein [CRP], magnesium), measurement of blood pressure, and Tanner staging were performed. MS was defined by International Diabetes Federation (IDF) and the National Cholesterol Education Program Third Adult Treatment Panel guidelines (NCEP ATP III) criteria, modified by Cook et al. (Arch Pediatr Adolesc Med. 2003;157:821-827) and Ford et al. (Diabetes Care. 2005;28:878-881). The median age of 76 survivors was 11.9 years (interquartile range [IQR]: 9.6-13.5). Twenty-four (32%) survivors were obese or overweight. The prevalence of insulin resistance (17%), hypertension (7%), hypertriglyceridemia (20%), and low HDL (37%) was comparable to the prevalence in children/adolescents in historical population-based studies from India. The prevalence of MS ranged from 1.3% to 5.2%, as per different defining criteria. Cranial radiotherapy, age at diagnosis, sex, or socioeconomic status were not risk factors for MS. The prevalence of MS in survivors of childhood ALL, at a median duration of 3 years from completion of chemotherapy, was comparable to the reference population. The prevalence of being obese or overweight was, however, greater than historical controls.

Growth in Children Treated for Acute Lymphoblastic Leukemia: Single Institution Report from North India.

Survivors of childhood leukemia are at risk of impaired growth and short stature as adults due to intensive combination chemotherapy and radiation injury. This study was undertaken to evaluate anthropometry in children treated for acute lymphoblastic leukemia (ALL). Children treated for ALL and off treatment for a minimum period of 2 years were evaluated for height, weight and BMI. Z scores were calculated for height, weight and BMI: at induction, 6 months after starting treatment, at end of treatment and at 2 years after completion of therapy. Change in z scores were calculated and compared with CDC criteria and Agarwal standards for Indian children. Fifty two boys and 21 girls were analyzed. Height and weight z scores were seen to show a steep decrease during the initial intensive phase of therapy. The gain in height and weight continued to be slow during therapy and catch up occurred after cessation of therapy. On completion of therapy, patients were shorter, but not significantly so. Girls <9 years were significantly shorter. Weight remained on the lower side of normal. Change of z scores was statistically significant for weight at end of treatment (p = 0.032) and 2 years after completion of treatment (p = 0.00). BMI z score increased throughout the study period. Peak growth velocities were also late in the study subjects Anthropometric variables of height, weight and BMI are affected by ALL during therapy. Growth deceleration is maximum during the intensive phase of therapy. Catch up growth occurs but children remain smaller than their peers.

Sociodemographic profile of children with Kawasaki disease in North India.

Kawasaki disease (KD) is now the commonest cause of acquired heart disease in children in developed countries. KD occurs all over the world, including developing countries. The present study steps out to explore our hypothesis, driven by clinical observation over the last 18 years, whether children with KD in North India are of a higher socioeconomic status than children with other rheumatologic diseases. One hundred consecutive children with KD, registered in Pediatric Rheumatology Clinic before January 2011, were enrolled as cases. Children with other rheumatologic diseases were taken as controls. Assessment of socioeconomic status was done by administering the Aggarwal scale. Data were collected through interview. Statistical analysis was done using SPSS package version 16. On univariate analysis, male sex, higher educational status of parents, urban residence, immunization status being complete, and higher scores on Aggarwal scale were found to be significantly associated with KD. On multivariate analysis, only male sex and urban residence were found to be significantly associated with KD (p < 0.001). Families of children with KD tend to have a better sociodemographic profile when compared with other pediatric rheumatologic disorders in North India. These results, however, need to be replicated in a multicentric study for any firm conclusions to be drawn.

Vertebral Scheuermann's disease in Europe: prevalence, geographic variation and radiological correlates in men and women aged 50 and over.

UNLABELLED: In 27 centres across Europe, the prevalence of deforming spinal Scheuermann's disease in age-stratified population-based samples of over 10,000 men and women aged 50+ averaged 8% in each sex, but was highly variable between centres. Low DXA BMD was un-associated with Scheuermann's, helping the differential diagnosis from osteoporosis. INTRODUCTION: This study aims to assess the prevalence of Scheuermann's disease of the spine across Europe in men and women over 50 years of age, to quantitate its association with bone mineral density (BMD) and to assess its role as a confounder for the radiographic diagnosis of osteoporotic fracture. METHODS: In 27 centres participating in the population-based European Vertebral Osteoporosis Study (EVOS), standardised lateral radiographs of the lumbar and of the thoracic spine from T4 to L4 were assessed in all those of adequate quality. The presence of Scheuermann's disease, a confounder for prevalent fracture in later life, was defined by the presence of at least one Schmorl's node or irregular endplate together with kyphosis (sagittal Cobb angle >40° between T4 and T12) or a wedged-shaped vertebral body. Alternatively, the (rare) Edgren-Vaino sign was taken as diagnostic. The 6-point-per-vertebral-body (13 vertebrae) method was used to assess osteoporotic vertebral shape and fracture caseness. DXA BMD of the L2-L4 and femoral neck regions was measured in subsets. We also assessed the presence of Scheuermann's by alternative published algorithms when these used the radiographic signs we assessed. RESULTS: Vertebral radiographic images from 4486 men and 5655 women passed all quality checks. Prevalence of Scheuermann's varied considerably between centres, and based on random effect modelling, the overall European prevalence using our method was 8% with no significant difference between sexes. The highest prevalences were seen in Germany, Sweden, the UK and France and low prevalences were seen in Hungary, Poland and Slovakia. Centre-level prevalences in men and women were highly correlated. Scheuermann's was not associated with BMD of the spine or hip. CONCLUSIONS: Since most of the variation in population impact of Scheuermann's was unaccounted for by the radiological and anthropometric data, the search for new genetic and environmental determinants of this disease is encouraged.

Renal failure due to granulomatous interstitial nephritis in native and allograft renal biopsies: experience from a tertiary care hospital.

Granulomatous interstitial nephritis is a rare cause of renal failure in both native and allograft renal biopsies. Drugs and sarcoidosis are the commonest causes of granulomatous interstitial nephritis as reported in Western countries. Unlike the west, tuberculosis is the commonest cause of granulomatous interstitial nephritis in Indian subcontinent. The etiological factors, clinical course, glomerular and tubulointerstitial changes associated with granulomatous interstitial nephritis have been analyzed in the present study along with the outcome in patients with granulomatous interstitial nephritis.

Vitamin D levels during and after resolution of ketoacidosis in children with new onset Type 1 diabetes.

AIM: To study the effect of ketoacidosis on measured 25-hydroxyvitamin D3 in children with new onset Type 1 diabetes. METHODS: Measurement of pH and bicarbonate levels was carried out in children with newly diagnosed Type 1 diabetes at presentation with ketoacidosis. 25-hydroxyvitamin D3 estimation was carried out at presentation (timepoint 1) and 1 month later (timepoint 2). There was no significant difference in the mean (±sd) 25-hydroxyvitamin D3 levels [35.39 (±25.79) vs 39.63 (±48.03) nmol/L; P = 0.661) at the two timepoints in the study. RESULTS: Correlation analysis revealed a positive correlation between bicarbonate levels and timepoint 1, i.e. the lower the bicarbonate levels, the lower were the timepoint 1 levels and vice versa (correlation coefficient 0.538, P = 0.001). Timepoint 2 levels also showed a positive correlation with serum bicarbonate levels with a correlation coefficient of 0.379 (P = 0.032). None of the variables other than bicarbonate,.(age, gender, BMI, pH or time), was found to have the predictive ability for timepoint1 levels. Similarly for predicting timepoint 2 levels, BMI was found to have independent predictive ability in addition to bicarbonate. CONCLUSIONS: Severe ketoacidosis, as judged by bicarbonate but not pH, may transiently lower 25-hydroxyvitamin D3 levels in children with new onset Type 1 diabetes. Persistence of low 25-hydroxyvitamin D3 levels after resolution of ketoacidosis suggests a state of permanent vitamin D deficiency in our patient population.