High prevalence of CFHR deletions in Indian women with pregnancy-associated hemolytic uremic syndrome.

AIM: Pregnancy-associated hemolytic uremic syndrome (P-aHUS) is an important cause of peripartum acute kidney injury. Studies from Europe have described mutations in complement regulator genes, and data in Indian patients is scarce. Hence this study used multiplex ligation-dependent probe amplification (MLPA) to identify variants in complement genes in P-aHUS patients. METHODS: We present 17 patients of P-aHUS who were investigated for complement protein levels and genetic analysis with MLPA for complement genes. Plasma exchange therapy was offered to all patients presenting in acute phase. RESULTS: Mean age 26.74 (3.36) years with 15/17 delivered by caesarean section. Eleven patients received early (within 7 days) plasma exchange, three were dialysis-dependent at 3 months and seven were dialysis-free. Only one of the three patients receiving late (after 7 days) plasma exchange was dialysis-free. MLPA showed that 11 patients had heterozygous deletions of exons 3, 5, 6 of CFHR1 and upstream region of exons 1, 2, 3, 6 and intron 4 of CFHR3 gene while four patients had homozygous deletions at the same loci. Two patients had no MLPA-detectable variations. CONCLUSION: This study reports a high proportion of deletions of exons of CFHR1 & CFHR3 genes in Indian P-aHUS patients detectable by MLPA by copy number variations. This needs confirmation in large multicentre studies. Plasma exchange can be an effective therapy in the non-availability of Eculizumab.

Renal Replacement Therapy in Adult Intensive Care Unit: An ISCCM Expert Panel Practice Recommendation.

Acute kidney injury (AKI) contributes significantly to morbidity and mortality in ICU patients. The cause of AKI may be multifactorial and the management strategies focus primarily on the prevention of AKI along with optimization of hemodynamics. However, those who do not respond to medical management may require renal replacement therapy (RRT). The various options include intermittent and continuous therapies. Continuous therapy is preferred in hemodynamically unstable patients requiring moderate to high dose vasoactive drugs. A multidisciplinary approach is advocated in the management of critically ill patients with multi-organ dysfunction in ICU. However, an intensivist is a primary physician involved in life-saving interventions and key decisions. This RRT practice recommendation has been made after appropriate discussion with intensivists and nephrologists representing diversified critical care practices in Indian ICUs. The basic aim of this document is to optimize renal replacement practices (initiation and management) with the help of trained intensivists in the management of AKI patients effectively and promptly. The recommendations represent opinions and practice patterns and are not based solely on evidence or a systematic literature review. However, various existing guidelines and literature have been reviewed to support the recommendations. A trained intensivist must be involved in the management of AKI patients in ICU at all levels of care, including identifying a patient requiring RRT, writing a prescription and its modification as per the patient's metabolic need, and discontinuation of therapy on renal recovery. Nevertheless, the involvement of the nephrology team in AKI management is paramount. Appropriate documentation is strongly recommended not only to ensure quality assurance but also to help future research as well. How to cite this article: Mishra RC, Sinha S, Govil D, Chatterjee R, Gupta V, Singhal V, et al. Renal Replacement Therapy in Adult Intensive Care Unit: An ISCCM Expert Panel Practice Recommendation. Indian J Crit Care Med 2022;26(S2):S3-S6.

Renal Replacement Therapy in Pregnancy-related Acute Kidney Injury: Getting the Timing Right.

Recent trials have failed to show a survival benefit from the early initiation of dialytic therapies in acute kidney injury (AKI), but the problem has not been studied in pregnancy-related AKI. While the KDIGO criteria have not been validated in pregnancy-related acute kidney injury (PRAKI), additionally both fetal and maternal outcomes require to be studied. The short observational study by Banerjee et al. contains some interesting observations. HOW TO CITE THIS ARTICLE: Lobo VA. Renal Replacement Therapy in Pregnancy-related Acute Kidney Injury: Getting the Timing Right. Indian J Crit Care Med 2020;24(8):624-625.

Renal Replacement Therapy in Acute Kidney Injury: Which Mode and When?

Renal replacement therapy (RRT) for acute kidney injury (AKI) patients in an intensive care unit (ICU) presents unique problems of providing biochemical and fluid removal in patients with unstable circulations, inotropes, and increased capillary permeability. Although no individual modality has been shown to confer a mortality benefit, it is assumed that continuous therapies like peritoneal dialysis (PD) and venovenous hemofiltration or hemodiafiltration may be better tolerated by the patient with hemodynamic instability, raised intracranial pressure (ICP), and liver failure. An individual patient may require more than one treatment in the course of his/her illness. The therapies offered may reflect available resources, local expertise, and cost constraints. HOW TO CITE THIS ARTICLE: Lobo VA. Renal Replacement Therapy in Acute Kidney Injury: Which Mode and When? Indian J Crit Care Med 2020;24(Suppl 3):S102-S106.

Prolonged intermittent renal replacement therapy in children.

Wide ranges of age and weight in pediatric patients makes renal replacement therapy (RRT) in acute kidney injury (AKI) challenging, particularly in the pediatric intensive care unit (PICU), wherein children are often hemodynamically unstable. Standard hemodialysis (HD) is difficult in this group of children and continuous veno-venous hemofiltration/dialysis (CVVH/D) has been the accepted modality in the developed world. Unfortunately, due to cost constraints, CVVH/D is often not available and peritoneal dialysis (PD) remains the common mode of RRT in resource-poor facilities. Acute PD has its drawbacks, and intermittent HD (IHD) done slowly over a prolonged period has been explored as an alternative. Various modes of slow sustained IHD have been described in the literature with the recently introduced term prolonged intermittent RRT (PIRRT) serving as an umbrella terminology for all of these modes. PIRRT has been widely accepted in adults with studies showing it to be as effective as CVVH/D but with an added advantage of being more cost-effective. Pediatric data, though scanty, has been promising. In this current review, we elaborate on the practical aspects of undertaking PIRRT in children as well as summarize its current status.

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.

Renal Microvascular Ischemia Secondary to Nonsteroidal Anti-inflammatory Drugs.

Nonsteroidal anti-inflammatory drugs (NSAIDs), widely prescribed for pain, can affect kidneys in various ways. We present a case of a 37-year-old woman with multiple NSAIDs intake over a short period for dysmenorrhea followed by the development of new-onset bilateral flank pain. Computed tomography revealed bilateral multiple renal infarcts. Renal function was normal. Investigations showed no cardiac or renal artery lesion and vasculitis work-up was negative. She was treated conservatively and further NSAID intake was avoided. Follow-up scan showed complete restoration of the blood flow in previously affected areas. Thus, microvascular ischemia secondary to NSAIDs was thought to be responsible.

Continuous Hemodiafiltration with the oXiris Filter Ameliorates Cytokine Storm and Induces Rapid Clinical Improvement in COVID-19 - A Case Report.

Delayed interferon secretion and cytokine dysregulation are responsible for the life-threatening acute respiratory distress syndrome (ARDS), multiorgan dysfunction and shock in COVID 19, which closely resembles secondary hemophagocytic lymphohistiocytosis (sHLH). IL-6, a marker of hypercytokinemia in patients with COVID-19 is positively correlated with disease severity, development and progression of ARDS, and mortality. Therapy to either reduce IL-6 or inhibit its action with either non-specific inhibitors of inflammation like dexamthasone or Toclizumab a specific inhibitor of IL-6 has produced decrease in mortality. We describe a novel method of treatment in a patient with multiorgan involvement in COVID 19, using the oXiris hemofilter which delivers renal replacement therapy while also reducing cytokines like IL-6.

Novel Mutations in the DGKE Gene in Two Indian Patients with Early-onset Atypical Haemolytic Uraemic Syndrome.

Atypical haemolytic uremic syndrome (aHUS) is a clinically and genetically heterogeneous condition caused by a complex interplay between genomic susceptibility factors and environmental influences. Pathogenic variants in the DGKE gene are recently identified in cases with infantile-onset autosomal recessive aHUS. The presence of low serum C3 levels, however, has rarely been described in cases of DGKE-associated aHUS. Molecular genetic testing was performed by a commercial next-generation sequencing (NGS) panel as well and by an in-house developed targeted NGS for DGKE gene. Copy number variations (CNVs) were computed from NGS data by calculating a normalised copy number ratio of aligned number of reads at targeted genomic regions against multiple reference regions of the same sample and multiple controls. We report here two such novel clinically relevant variants (c.727_730delTTGT and c.251_259delGCGCCTTC) in the DGKE gene, in two families of infantile aHUS with low serum C3 levels.

Increased serum catalytic iron may mediate tissue injury and death in patients with COVID-19.

The pathophysiology and the factors determining disease severity in COVID-19 are not yet clear, with current data indicating a possible role of altered iron metabolism. Previous studies of iron parameters in COVID-19 are cross-sectional and have not studied catalytic iron, the biologically most active form of iron. The study was done to determine the role of catalytic iron in the adverse outcomes in COVID-19. We enrolled adult patients hospitalized with a clinical diagnosis of COVID-19 and measured serum iron, transferrin saturation, ferritin, hepcidin and serum catalytic iron daily. Primary outcome was a composite of in-hospital mortality, need for mechanical ventilation, and kidney replacement therapy. Associations between longitudinal iron parameter measurements and time-to-event outcomes were examined using a joint model. We enrolled 120 patients (70 males) with median age 50 years. The primary composite outcome was observed in 25 (20.8%) patients-mechanical ventilation was needed in 21 (17.5%) patients and in-hospital mortality occurred in 21 (17.5%) patients. Baseline levels of ferritin and hepcidin were significantly associated with the primary composite outcome. The joint model analysis showed that ferritin levels were significantly associated with primary composite outcome [HR (95% CI) = 2.63 (1.62, 4.24) after adjusting for age and gender]. Both ferritin and serum catalytic iron levels were positively associated with in-hospital mortality [HR (95% CI) = 3.22 (2.05, 5.07) and 1.73 (1.21, 2.47), respectively], after adjusting for age and gender. The study shows an association of ferritin and catalytic iron with adverse outcomes in COVID-19. This suggests new pathophysiologic pathways in this disease, also raising the possibility of considering iron chelation therapy.

Atypical HUS Associated with CFH/CFHR-1 Hybrid Gene.

Atypical hemolytic uremic syndrome is a rare form of thrombotic microangiopathy caused by complement pathogenic variants. We describe a case of a 33-year-old woman who presented as rapidly progressing renal failure requiring dialysis and had anemia, microhematuria, low C3, normal C4 levels, and normal platelet count. Renal biopsy revealed arteriolar thrombotic microangiopathy and acute tubular injury. Patient was treated with plasma exchange and hemodialysis as required. This resulted in partial recovery at 1 month. Genetic workup by multiplex ligation-dependent probe amplification revealed a 1.5 times higher signal intensity on downstream region of CFH gene and 50% reduced intensity of exon 6 of CFHR1 gene, suggesting a gene conversion event, similar to those previously reported from Spain and Portugal.

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.

Inadvertently high dialysate magnesium causing weakness and nausea in hemodialysis patients.

As maintenance hemodialysis patients are exposed to large quantities of dialysis water, any contamination of it might be reflected in plasma levels. We present a series of cases due to such a contamination. Six maintenance hemodialysis patients dialyzing at the same peripheral hemodialysis facility presented to us over a short period of time with symptoms mimicking inadequate dialysis. Their blood urea and creatinine levels were not very high, but all the patients had hypermagnesemia [serum Mg levels = 1.8 (±0.3) mmol/L]. Except for one patient who had cardiac arrest at presentation, all patients improved after undergoing hemodialysis at our center [serum Mg at discharge = 0.86 (±0.01) mmol/L]. The origin of hypermagnesemia was traced to dialysis water contamination with magnesium due to inadequate maintenance of the water treatment system. Corrective measures improved the quality of water, and no further cases were reported from that center. Proper maintenance and periodic checks of the quality of water are central to the outcomes of maintenance hemodialysis patients.

Feasibility of sustained low efficiency dialysis in critically sick pediatric patients: A multicentric retrospective study.

INTRODUCTION: Sustained low-efficiency dialysis (SLED) has emerged as a cost effective alternative to Continuous Renal Replacement Therapy in the management of hemodynamically unstable adult patients with acute kidney injury. The objective of the study was to document the SLED practices in these centers, and to look at the feasibility, and tolerability of SLED in critically sick pediatric patients. METHODS: It was a retrospective record review from January 2010 to June 2016 done in four tertiary pediatric nephrology centers in India. All pediatric patients undergoing SLED in the collaborating centers were included in the study. Basic demographic data, prescription parameters and outcomes of patients were recorded. FINDINGS: During the study period a total of 68 children received 211 sessions of SLED. PRISM score at admission in patients was 13.33 ± 9.15. Fifty-seven patients were ventilated (84%). Most of the patients had one or more organ system involved in addition to renal (n = 64; 94%). Heparin free sessions were achievable in 153 sessions (72%). Out of 211 sessions, 148 sessions were on at least one inotrope (70.1%). Overall premature terminations had to be done in 27 sessions (13% of all sessions), out of which 7 sessions had to be terminated due to circuit clotting (3.3%). Intradialytic hypotension or need for inotrope escalation was seen in 31 (15%) sessions but termination of the session for drop in BP was required in only 20 (9%) sessions. CONCLUSION: SLED is a feasible method of providing renal replacement in critically ill pediatric patients.

Vascular Access Creation and Care--Perspective From India.

India has one of the fastest growing economies in the world and is home to nearly one sixth of world's population. Chronic diseases such as diabetes mellitus and hypertension are common. Kidney disease is a known complication of these chronic diseases and is on the rise. Improving affordability with advanced care delivery has led to the increasing use of maintenance hemodialysis. Along with this hemodialysis comes the inevitable need for vascular access. Interventional nephrology in India is a fast-evolving discipline and promises to be a critical component of hemodialysis care in the future. This review provides a background on the current state of the CKD burden in India and the various vascular access options in use currently. In addition, we describe the experience of 2 centers in western and southern India in managing vascular access needs in hopes that they will serve as a model of the proliferation of vascular access care throughout India and in other developing countries.

Enzymuria pattern in early post renal transplant period: Diagnostic usefulness in graft dysfunction.

Serum creatinine does not distinguish between various causes of graft dysfunction. Serial assay of proximal tubular enzymes N-Acetyl-D-glucosaminidase (NAG), Alanine aminopeptidase (AAP) and Gamma glutamyl transferase (GGT) in urine was done to assess their usefulness in distinguishing various causes of graft dysfunction. Daily serum creatinine and enzymuria were measured in 32 consecutive renal allograft recipients for first 15 postoperative days. Graft dysfunction was defined as >20% increase in serum creatinine and >100% increase in enzymuria over the baseline. The diagnosis of graft dysfunction was based upon clinical criteria, ultrasonography, cyclosporin trough level, allograft biopsy, response to anti-rejection therapy and alteration of cyclosporin dosage. Fifteen episodes of graft dysfunction were identified in 15 patients. The sensitivity and specificity of the enzymes (NAG, AAP and GGT) for predicting graft dysfunction were 87.5%, 86.9%, 88.5% and 98.2%, 98.2%, 97.9% respectively. There was a significant increase in enzymuria during acute tubular necrosis (ATN) and acute rejection episode compared to cyclosporin nephrotoxicity (p<0.01). Enzymuria assay provides a simple, reliable and noninvasive method to distinguish cyclosporin nephrotoxicity from acute tubular necrosis and acute rejection in renal allograft recipients.