Pulmonary renal syndrome secondary to malignant hypertension.

A man in his early 30s presented with sudden-onset respiratory distress, haemoptysis and reduced urine output. He was in volume overload with a blood pressure recording of 240/180 mm Hg. Pulmonary renal syndrome was suspected and he was initiated on plasmapheresis, followed by steroid pulse therapy. Chest radiography and the presence of fragmented red cells on the peripheral smear were unexplained. These were later explained by hypertensive nephropathy and thrombotic microangiopathy changes on renal biopsy. His respiratory and haematological parameters improved with blood pressure control. Malignant hypertension closely resembles pulmonary renal syndrome, which must be remembered in order to avoid plasmapheresis and high-dose immunosuppressive therapy.

Current updates on metabolites and its interlinked pathways as biomarkers for diabetic kidney disease: A systematic review.

Diabetic kidney disease (DKD) is a major microvascular complication of diabetes mellitus (DM) that poses a serious risk as it can lead to end-stage renal disease (ESRD). DKD is linked to changes in the diversity, composition, and functionality of the microbiota present in the gastrointestinal tract. The interplay between the gut microbiota and the host organism is primarily facilitated by metabolites generated by microbial metabolic processes from both dietary substrates and endogenous host compounds. The production of numerous metabolites by the gut microbiota is a crucial factor in the pathogenesis of DKD. However, a comprehensive understanding of the precise mechanisms by which gut microbiota and its metabolites contribute to the onset and progression of DKD remains incomplete. This review will provide a summary of the current scenario of metabolites in DKD and the impact of these metabolites on DKD progression. We will discuss in detail the primary and gut-derived metabolites in DKD, and the mechanisms of the metabolites involved in DKD progression. Further, we will address the importance of metabolomics in helping identify potential DKD markers. Furthermore, the possible therapeutic interventions and research gaps will be highlighted.

Non-cuffed central venous catheter for unplanned and urgent start haemodialysis in chronic kidney disease: A multi-centre experience from India.

BACKGROUND: Central Venous Catheter (CVC) is indispensable to unplanned and urgent start haemodialysis in chronic kidney disease (CKD). While cuffed CVC is preferred to non-cuffed CVC for urgent start haemodialysis, patient's clinical condition might warrant immediate insertion of non-cuffed CVC. In the resource poor setting, non-cuffed CVCs might have to be retained longer than guideline recommended limit of 2 weeks. In this multi-centre retrospective observational study, the real-world survival of non-cuffed CVC was assessed among CKD patients who initiated dialysis urgently. METHODS: CVC survival was assessed by Kaplan-Meier survival estimate. Predictors of premature CVC loss were assessed using multi-level multi-variate Cox frailty model wherein, each centre was provided with a random intercept to account for within-centre correlation of practice patterns. RESULTS: Among 433 non-cuffed CVCs, there were 393 removals out of which 80% were elective and 20% were premature. The median CVC survival was 37 days (95% CI: 35-41). The rate of premature CVC removal was 4.5/1000 CVC-days (95% CI: 3.6-5.6). Mechanical complications followed by central line associated blood stream infection (CLABSI) were the most common reasons for premature removal. Rate of CLABSI was 1.7/1000 CVC-days (95% CI: 1.2-2.5). Diabetic CKD significantly increased the hazard of premature CVC removal (HR 1.91, 95% CI: 1.01-3.63, p = 0.04) while right internal-jugular location decreased the hazard (HR 0.22, 95% CI: 0.13-0.38, p < 0.001). CONCLUSION: Prolonged retention of non-cuffed CVC (median 37 days) is common in resource-poor setting. It is worrisome and calls for pre-emptive access creation.

Phaeohyphomycosis in Renal Transplant Recipients: A Case Series.

Phaeohyphomycosis is a rare fungal infection in renal transplant recipients. We describe here five cases of phaeohyphomycosis in renal transplant recipients, two with deep-seated unusual sites of infection. All patients received antifungals, and surgical excision was done where feasible. Outcomes included complete resolution of infection in three, partial resolution in one, and mortality in one case.

Clinical profile and outcomes of COVID-19 patients with acute kidney injury: a tertiary centre experience from South India.

AIM: The rates of development of acute kidney injury (AKI) in COVID-19 have been variably reported from across the world. Prevalence and outcomes of AKI in hospitalised COVID-19 patients in India has not been studied well. METHODS: This was a retrospective observational study amongst adult hospitalised COVID-19 patients admitted at a tertiary care centre between May 1 and October 31, 2020. We estimated the prevalence of AKI and outcomes including mortality and acute kidney disease (AKD) at the time of discharge. Regression analysis was done to study the factors associated with mortality and AKD. RESULTS: Out of 2650 hospitalised patients with COVID-19, 190 (7.2%) patients developed AKI. Mean age of patients with AKI was 62.6 years, 81.6% were male. Comorbidities included diabetes mellitus in 72.1%, hypertension in 66.8%, heart disease in 30% and chronic kidney disease (CKD) in 22.6%. Most patients had stage 1 AKI (71.1%). Overall mortality in patients with AKI was 22.1%, 75% in those requiring dialysis and 74.5% in those requiring ICU. Amongst survivors without pre-existing CKD, 40.9% patients had acute kidney disease at the time of discharge. Higher age, stage 3 AKI and need for mechanical ventilation were associated with higher mortality. On multivariable regression, factors associated with AKD at discharge included pre-existing heart disease and severe albuminuria during hospitalisation. CONCLUSION: In our study population, we found a low prevalence of AKI. Mortality was high in AKI patients requiring ICU care and dialysis. Amongst survivors, a significant percentage had AKD at the time of discharge.

Computational validation of ABCB1 gene polymorphism and its effect on tacrolimus dose concentration/levels in renal transplant individuals of South India.

Patients with end-stage renal failure require hemodialysis and peritoneal dialysis; however, kidney transplantation is considered a better treatment option for renal failure patients, improving their quality of life and longevity. Among several potent immunosuppressive agents, tacrolimus (TAC) has shown progressive improvement in the graft survival rates after renal transplantation. Fifty kidney transplant patients undergoing TAC immunosuppressive treatment were included. The human genomic DNA was isolated using the phenol-chloroform extraction procedure. CYP3A5*6, CYP3A5*2, and ABCB1 exon 21 G2677 T/A polymorphisms were genotyped using the polymerase chain reaction-restriction fragment length polymorphism method. Fisher's exact test and Chi-square analysis were performed to analyze the data, where p < 0.05 was considered statistically significant. In addition, we implemented bioinformatics studies on ABCB1 protein to determine the mutation's effect sequentially and structurally. Among the genotyped single nucleotide polymorphisms (SNPs), SNPs of CYP3A5*2 and CYP3A5*6 did not vary in the studied population. The concentration/dose (C/D) ratio of TT genotype of the ABCB1 gene was higher (95% CI: 177.38-269.46) when compared to TA and AA. However, there were no substantial differences between the ABCB1 genotypes and TAC C/D ratio (p = 0.953). The TAC dose mg/kg/day (p = 0.002) and C/D ratio (p = 0.004) exhibited a statistically significant difference. However, no significant difference was found with respect to the ABCB1 gene between the non-toxicity and toxicity groups. Mutation and residue interaction analysis results showed that the S893T mutation destabilizes the ABCB1 protein, thus reducing the protein's flexibility. The present study demonstrated a substantial relationship between the TAC dose and C/D ratio, including the non-toxicity and toxicity groups. However, no possible correlation was observed between the ABCB1 gene polymorphism and renal transplant.

Prevalence and outcome of systemic fungal infections in renal transplant recipients - A tertiary care experience.

Fungal infections are an important cause of morbidity and mortality in renal transplant recipients. These infections account for 5% of all infections in renal transplant recipients. The symptoms of systemic fungal infections are nonspecific, particularly in their early stages, and this can lead to delay in diagnosis. Retrospective analysis was conducted on all renal transplants that were performed at our center over a 20-year period from 1996-2016. Cases of invasive fungal infections (IFIs) that occurred among renal transplant recipients were identified to describe the epidmeiology of these infections. A total of 67 (9.2%) IFI cases were identified among 725 renal transplant recipients. Of the 67 patients (9.24%) with IFI, 31 (46.2%) cases were seen in deceased donor transplant recipients. Of 67 cases with IFI, 42 (62.7%) had received induction therapy. The incidence of fungal infections according to the induction agent used was, 14.3% with basiliximab, 12.3% each with daclizumab and rabbit antithymocyte globulin, and 6.3% among patients not given any induction. Invasive candidiasis was the most common IFI overall, followed by mucormycosis, invasive aspergillosis, and cryptococcosis. Median time to onset of IFI was 117.9 days. Majority of infections occurred within 180 days after transplantation. Late posttransplant (>180 days after transplantation) IFI's were predominantly caused by Candida, followed by Cryptococcus. The longest time to infection was a case of histoplasma, occurring seven years posttransplant. The overall 12-month cumulative incidence (CI) for any IFI was 9.1%. The 12-month CI of the first IFI increased from 7.3% between 1996 and 2001 to 10.5% between 2010 and 2016. The overall mortality rate was 38.8%. The use of newer and more-effective immunosuppressive agents in recent years are associated with increased rates of fungal infections in renal transplant recipients. Therefore, early detection of fungal infections and proper therapy are important in improving survival and reducing mortality.

Successful Tenckhoff catheter salvage in a patient with peritoneovesical fistula: A case report.

INTRODUCTION: Many techniques are available for inserting peritoneal dialysis (PD) or continuous ambulatory peritoneal dialysis (CAPD) catheters, with varying possible complications. We report a case of bladder perforation that was managed with catheter salvage. CASE REPORT: A 48-year-old man with end-stage renal disease (ESRD) underwent CAPD catheter placement percutaneously, with tip in the pelvis. On the 3rd day after placement, the patient complained of increase in urinary volume with PD flushing. Urine analysis showed 3(+) glucose and absent creatinine. Cystogram showed the catheter abutting the bladder wall. CT of the abdomen showed the catheter piercing the bladder and exiting through the posterior wall. The PD catheter was repositioned under fluoroscopy. DISCUSSION: The complications surrounding insertion of CAPD catheter can be either mechanical or infectious. Peritoneo-vesical fistula or placement of the PD catheter into the urinary bladder is a very rare complication. The possibility of catheter salvage should be entertained while discussing management options.

Association between end-stage diabetic nephropathy and MTHFR (C677T and A1298C) gene polymorphisms.

AIM: Methylenetetrahydrofolate reductase (MTHFR) is a regulatory enzyme of homocysteine metabolism. The C677T and A1298C polymorphism of the MTHFR gene has been reported to be associated with elevated plasma homocysteine in patients with Diabetic nephropathy. This study aimed to investigate the influence of the C677T and A1298C polymorphisms on the progression chronic kidney disease in diabetic nephropathy of south Indian population. METHODS: We genotyped 145 DN cases and 100 controls for the C677T and A1298C polymorphisms using PCR-RFLP based protocols, and all diabetic nephropathy cases divided into two groups based on CKD stages: 60 DN cases were early stage (CKD1 to CKD3) and 85 DN cases were advanced stage (CKD4 and CKD5). Association χ2 and univariate analysis were performed. RESULTS: The C677T (OR = 4.2; 95% CI = 2.31-7.64 and P = 0.001) and A1298C (OR = 2.8; 95% CI = 1.05-7.57 and P = 0.033) polymorphism was shown that the significant association between the cases and control. Furthermore, the MTHFR gene polymorphism C677T (OR = 2.48; 95% CI = 1.25-4.9 and P = 0.008) was observed that the significant contribution of the progression of CKD in DN. CONCLUSION: These findings suggest that the C677T and A1298C polymorphism of MTHFR gene was associated with diabetic nephropathy in a south Indian population. Furthermore, the present study provides evidence that the C677T polymorphism was associated with CKD progression in DN.

Aldosterone synthase gene is not a major susceptibility gene for progression of chronic kidney disease in patients with autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common heritable kidney disease and is characterized by bilateral renal cysts. Hypertension is a frequent cause of chronic kidney disease (CKD) and mortality in patients with ADPKD. The aldosterone synthase gene polymorphisms of the renin-angiotensin-aldosterone system have been extensively studied as hypertension candidate genes. The present study is aimed to investigate the potential modifier effect of CYP11B2 gene on the progression of CKD in ADPKD. One hundred and two ADPKD patients and 106 healthy controls were recruited based on Ravine inclusion and exclusion criteria. The three tag-SNPs within CYP11B2 gene (rs3802230, rs4543, and rs4544) were genotyped using FRET-based KASPar method. Cochran-Armitage trend test was used to assess the potential associations between these polymorphisms and CKD stages. Mantel- Haenszel stratified analysis was used to explore confounding and interaction effects of these polymorphisms. Of the three tag-SNPs genotyped, rs4544 polymorphism was monomorphic and rs3802230 deviated Hardy-Weinberg equilibrium. The CYP11B2 tag-SNPs did not show significant association with ADPKD or CKD. Further, these polymorphisms did not exhibit confounding effect on the relationship between CKD progression and hypertension. Our results suggest that aldosterone synthase gene is not a major susceptibility gene for progression of CKD in South Indian ADPKD patients.

Influence of angiotensin converting enzyme (ACE) gene rs4362 polymorphism on the progression of kidney failure in patients with autosomal dominant polycystic kidney disease (ADPKD).

BACKGROUND & OBJECTIVES: Autosomal dominant polycystic kidney disease (ADPKD) is an inherited systemic disorder, characterized by the fluid filled cysts in the kidneys leading to end stage renal failure in later years of life. Hypertension is one of the major factors independently contributing to the chronic kidney disease (CKD) progression. The renin-angiotensin aldosterone system (RAAS) genes have been extensively studied as hypertension candidate genes. The aim of the present study was to investigate the role of angiotensin converting enzyme tagging - single nucleotide polymorphisms (ACE tag-SNPs) in progression of CKD in patients with ADPKD. m0 ethods: In the present study six ACE tagSNPs (angiotensin converting enzyme tag single nucleotide polymorphisms) and insertion/deletion (I/D) in 102 ADPKD patients and 106 control subjects were investigated. The tagSNPs were genotyped using FRET-based KASPar method and ACE ID by polymerase chain reaction (PCR) and electrophoresis. Genotypes and haplotypes were compared between ADPKD patients and controls. Univariate and multivariate logistic regression analyses were performed to assess the effect of genotypes and hypertension on CKD advancement. Mantel-Haenszel (M-H) stratified analysis was performed to study the relationship between different CKD stages and hypertension and their interaction. RESULTS: All loci were polymorphic and except rs4293 SNP the remaining loci followed Hardy-Weinberg equilibrium. Distribution of ACE genotypes and haplotypes in controls and ADPKD patients was not significant. A significant linkage disequilibrium (LD) was observed between SNPs forming two LD blocks. The univariate analysis revealed that the age, hypertension, family history of diabetes and ACE rs4362 contributed to the advancement of CKD. INTERPRETATION & CONCLUSIONS: The results suggest that the ACE genotypes are effect modifiers of the relationship between hypertension and CKD advancement among the ADPKD patients.

Renin gene rs1464816 polymorphism contributes to chronic kidney disease progression in ADPKD.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a monogenic disorder and is a common genetic cause of chronic renal failure in children and adults. The enzyme renin plays a key role in the RAAS cascade and an important role in the development of hypertension and progression of renal disease in ADPKD. The present study is aimed to investigate the potential modifier effect of REN gene polymorphisms on the progression of chronic kidney disease (CKD) in ADPKD. METHODS: We analyzed 102 ADPKD patients and 106 healthy controls from the same geographic area. FRET-based KASPar single-nucleotide polymorphism (SNP) genotyping assays for REN gene tag-SNPs (rs2887284, rs2368564, rs1464816, rs7521667, rs10900555, rs6693954, rs6676670 and rs11571078) were performed. Cochran-Armitage trend test was used to assess the potential associations between these polymorphisms and CKD stages. Haplotype frequencies and LD measures were estimated by using the software Haploview. Mantel-Haenszel stratified analysis was used to explore confounding and interaction effects of these polymorphisms. RESULTS: Of the eight tag-SNPs genotyped, the rs10900555 polymorphism deviated from the Hardy-Weinberg equilibrium in controls. The presence of ADPKD in general was not significantly associated with the REN tag-SNPs included in this study. Linkage disequilibrium analysis yielded three haplotype blocks and the haplotypes of the respective blocks are not statistically different between ADPKD and controls. In multivariate analysis, the rs1464816 TG genotype showed a significant association with the advancement of CKD in ADPKD (OR = 4.80; 95 % CI = 1.30-17.82; p = 0.019). CONCLUSIONS: The present study provides evidence that the rs1464816 polymorphism in REN is associated with CKD progression in ADPKD.

Endothelin 1 gene is not a major modifier of chronic kidney disease advancement among the autosomal dominant polycystic kidney disease patients.

Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the presence of numerous cysts in the kidney and manifest with various renal and extra-renal complications leading to ESRD. Endothelin may contribute to various renal and extra-renal manifestations pointing to genetic and environmental modifying factors that alter the risk of developing chronic kidney disease (CKD) in ADPKD. In the present study we investigated six genes coding for endothelin 1 ( EDN1 ) tagging-single nucleotide polymorphisms (tag-SNPs) to unravel the EDN1 gene modifier effect for renal disease progression in ADPKD. Materials and Methods: The tag-SNPs were genotyped using FRET-based KASPar method in 108 ADPKD patients and 119 healthy subjects. Cochran-Armitage trend test was used to determine the association between ADPKD and EDN1 tag-SNPs. Multivariate logistic regression analysis was performed to assess the effect of tag-SNPs on CKD progression. The relationship between different CKD stages and hypertension and their interaction Mantel-Haenszel stratified analysis was performed. Results: All loci are polymorphic and followed Hardy-Weinberg equilibrium. Distribution of EDN1 genotypes and haplotypes in control and ADPKD is not statistically significant. Five SNPs covering 3.4 kb forming single LD block, but the LD was not strong between SNPs. The EDN1 genotypes are not contributing to the CKD advancement among the ADPKD patients. Conclusion: These results suggest that the EDN1 gene is not a major modifier of CKD advancement among ADPKD patients.

Pathways, perspectives and pursuits in polycystic kidney disease.

Polycystic kidney disease (PKD) is characterized by the growth of numerous cysts in the kidneys. When cysts form in the kidneys, they are filled with fluid. PKD cysts can profoundly enlarge the kidneys while replacing much of the normal structure, resulting in reduced kidney function and leading to kidney failure. Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary disease that occurs in one out of 1000 humans. PKD and its causes are being dissected through studies of human populations and through the use of animal models. Mouse models in particular have made a substantial contribution to our understanding of the gene pathways involved in the pathogenesis and the nature of signaling molecules that act in a tissue-specific manner at critical stages of cyst development. PKD has a number of characteristics that make it uniquely challenging for the development of therapies to slowdown disease progression. This review provides current understanding of the etiopathology, pathways involved and therapeutic targets of PKDs.

Curvularia lunata, a rare fungal peritonitis in continuous ambulatory peritoneal dialysis (CAPD); a rare case report.

Peritonitis is an inflammation of the peritoneum that occurs in patients with end-stage renal disease (ESRD) treated by peritoneal dialysis. Fungal peritonitis is a dreaded complication of peritoneal dialysis. Curvularia lunata is known to cause extra renal disease like endocarditis, secondary allergic bronchopulmonary aspergillosis and endophthalmitis. This case report presents a case of continuous ambulatory peritoneal dialysis peritonitis with this disease and its management. This case is of a 45-year-old man, presented with ESRD, secondary to diabetic nephropathy. After 3 months of hemodialysis the patient was put on continuous ambulatory peritoneal dialysis (CAPD). Local Examination at catheter site showed skin excoriation and purulent discharge. Further peritoneal dialysis (PD) fluid analysis showed neutrophilic leukocytosis and diagnosis of Curvularia lunata PD peritonitis.

Angiotensinogen gene polymorphisms and progression of chronic kidney disease in ADPKD patients.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a multisystemic and progressive disorder characterized by cyst formation and kidney enlargement and ultimately renal failure. Reduction of CKD progression in the ADPKD by pharmacological blockade of the renin-angiotensin-aldosterone system (RAAS) using ACE inhibitors indicated the involvement of RAAS pathway in the progression of CKD. The aim of the present study is to investigate the role of angiotensinogen tag-single nucleotide polymorphisms (AGT tag-SNPs) in progression of CKD. METHODS: Twelve AGT tag-SNPs were genotyped in 102 ADPKD patients and 106 non-ADPKD subjects using FRET-based KASPar method. Genotypes and haplotypes were compared between ADPKD and controls. The effect of genotypes and hypertension on CKD progression was assessed using univariate and multivariate logistic regression. Mantel-Haenszel (M-H) stratified analysis was performed to study the interaction between CKD stages and hypertension. RESULTS: Of the twelve tag-SNPs analyzed, only rs11122578 SNP deviated Hardy-Weinberg equilibrium in controls. Significant association between two AGT polymorphisms (rs11122577 and rs4762) and ADPKD was observed. Analysis of linkage disequilibrium revealed two haplotype blocks and haplotypes are not associated with ADPKD. The univariate analysis revealed that the age, hypertension, family history of diabetes and AGT rs4762 contributed to the progression of CKD in ADPKD. The modifier effect of these factors remained even after controlling other variables in multivariate analysis. CONCLUSIONS: The results of our study suggest significant association between Thr207Met polymorphism of AGT and CKD progression and acts as an effect modifier of renal disease progression in ADPKD.

Role of endothelial nitric oxide synthase VNTR (intron 4 a/b) polymorphism on the progression of renal disease in autosomal dominant polycystic kidney disease.

INTRODUCTION: Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder, and it is mainly associated with renal cyst formation. Several studies have also shown that these mutations regulate the physiology of epithelial tissues and determine renal cyst formation and growth in polycystic kidney disease (PKD). Nitric oxide (NO) is also considered to be an important factor involved in the deterioration of renal function. OBJECTIVES: The aim of the current study is to determine the frequency of NOS3 27-bp VNTR in ADPKD patients and to investigate the role of NOS3 27-bp VNTR genotypes in the modification of progression of renal disease in ADPKD. PATIENTS AND METHODS: The hypothesis was investigated by studying the South Indian population of 53 ADPKD patients and 94 unrelated healthy controls. The genotyping was performed by polymerase chain reaction and electrophoresis. Genotypes were compared between ADPKD and controls using the χ(2)-test. Univariate and multivariate logistic regression analyses were performed to assess the effect of genotypes and hypertension on the progress of chronic kidney disease (CKD). A stratified analysis was also performed to assess the evidence of the modification of hypertension-CKD relationship among VNTR genotypes. RESULTS: The NOS3 4a allele frequencies were 21.3% and 13.2% respectively for controls and ADPKD groups. The NOS3 VNTR genotypes and alleles were not associated with ADPKD. The univariate analysis showed that age, hypertension and NOS3 VNTR influenced the advancement of CKD. CONCLUSION: The present study confirms the significant association between the 27-bp VNTR and CKD advancement among the ADPKD patients in the South Indian population.

Role of renin-angiotensin-aldosterone system gene polymorphisms and hypertension-induced end-stage renal disease in autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited disease of the kidneys and is marked by progressive cyst growth and decline in kidney function, resulting in end-stage renal disease (ESRD). Hypertension is thought to be a significant modifying factor in the progression of renal failure in ADPKD. A number of genetic variations involved in renin-angiotensin-aldosterone system (RAAS) pathway genes have clinical or physiological impacts on pathogenesis of hypertension-induced ESRD in ADPKD. Information on RAAS pathway gene polymorphisms and their association with ESRD and ADPKD, published till March 2013, was collected using MEDLINE search. The present review deals with RAAS gene polymorphisms focused on hypertension-induced ESRD in ADPKD in different populations. The results were inconclusive and limited by heterogeneity in the study designs and the population stratification. In lieu of applying next generation sequencing technologies to study complex diseases, it is also possible to apply the same to unravel the complexity of ESRD in ADPKD.