Skin Colonizers and Catheter Associated Blood Stream Infections in Incident Indian Dialysis Patients.

Introduction: Skin colonization is a risk factor for multi-drug resistant (MDR) catheter-associated bloodstream infections (CABSI). This study aimed to determine the prevalence and spectrum of skin colonizing MDR organisms in incident HD patients and their correlation with CABSI. Methods: This single-center prospective cohort study included consecutive adult incident HD patients who underwent tunneled or non-tunneled internal jugular vein HD catheter insertion between June 1, 2017 and October 31, 2017. Nasal, axillary, and exit site swabs were obtained prior to catheter insertion, at 14-21 days, and 28-35 days after catheter insertion. Results: Forty-three patients (69.7% male, 32.5% diabetic) were included and provided baseline swabs, while 29 and 10 patients respectively were available for follow-up swabs. MDR bacterial colonization, MRSA colonization, and MDR gram-negative colonization on the baseline set of swabs were seen in 76.7%, 69.7%, and 9.3% patients respectively. Of the 29 patients with at least two consecutive sets of swabs, 79.3% showed persistent colonization by MDR gram-positive organisms, most commonly by MRSA. Six patients developed a CABSI during the follow-up period (incidence rate 3.7 per 1000 patient days), 83.4% were gram negative, and in only one instance (16.6%) was the bacterial strain identical to that which had previously colonized the skin. Conclusions: Three-fourths of HD patients were colonized by MDR bacteria prior to HD initiation. Despite the majority being persistently colonized by MDR gram-positive organisms, CABSIs were predominantly gram negative.

Difficult cannulation of hemodialysis arteriovenous fistula - Role of imaging in access management (DICAF STUDY).

BACKGROUND: Difficulty in cannulation of arteriovenous fistula (AVF) can lead to inadequate dialysis, transient to permanent loss of access and increases dependency on bridging catheters. This study aimed to analyze the causes for difficult fistula cannulation, using various imaging modalities. METHODOLOGY: This was a retrospective single-center observational study conducted between October 2017 and June 2018. Patients whose fistulae were difficult to cannulate were initially evaluated by physical examination followed by doppler ultrasonography or/and fistulogram as necessary. The patients were divided into two groups that is, primary difficult cannulation (within first three months of creation of fistula) or secondary difficult cannulation (after three months). RESULTS: We encountered difficult cannulation in 43 patients. About 60% were primary difficult cannulations. Most common causes for difficulty in cannulation were cannulation zone (CZ) stenosis (23.3%), immature fistula (20.9%), outflow stenosis (18.6%), inflow stenosis (11.6%), anatomical abnormalities (11.6%), outflow plus CZ stenosis (9.3%) and inflow plus CZ stenosis (4.7%). Among patients with primary difficult cannulation, immature fistula (34.6%) was the most common cause, whereas CZ stenosis (47.1%) was the most common etiology for secondary difficult cannulation. Edema leading to difficult cannulation was found in 12 patients (27.9%), all of which was due to central vein stenosis. Cannulation resulted in hematoma, fistula thrombosis, failure of fistula and pseudoaneurysm in 83.7%, 27.9%, 16.3%, and 2.3% of cases respectively. Bridging temporary dialysis catheter placement was required in 67.4% patients. Ultrasound doppler had lower diagnostic value when compared to fistulogram (71.4% vs 93.9%, p = 0.014). CONCLUSION: Difficulty in cannulating the arteriovenous fistula is a common problem in hemodialysis patients. We suggest that patients whose fistulae are difficult to cannulate should undergo early radiological evaluation to decrease catheter dependency and access failure.

Blind Bedside Peritoneal Dialysis Catheter Repositioning: An Innovative Technique.

Catheter malfunction in peritoneal dialysis (PD) patients may lead to technique failure. Surgical repositioning is sometimes required for resumption of PD and is associated with additional costs of procedure and hospitalization. Meanwhile, patients may need hemodialysis via a temporary vascular catheter with increasing costs and risk of catheter-associated bacteremia. We describe an innovative technique of blind bedside PD catheter repositioning as a possible alternative to surgical repositioning when there is catheter malfunction. In 29 patients over a period of 3 years, we attempted blind bedside PD catheter repositioning with immediate successful inflow and outflow in all of them after repositioning. At 1 month, 21 (72.4%) patients had good catheter function and at 6 months, 19 (65.5%) patients were continuing successful PD. This bedside innovative procedure allowed for catheter salvage without constructing a new exit site or tunnel and without the requirement of a break-in period. The benefits to the patient in terms of cost and shortened hospital stay make it ideal for resource-poor settings. We suggest that this innovative technique be attempted before resorting to the open surgical method of PD catheter repositioning.

Does Hemodialysis Need to be Initiated to Improve Platelet Function in CKD G5 Patients? A Pilot Prospective, Observational Cohort Study.

INTRODUCTION: We previously showed that patients with chronic kidney disease (CKD) Stage G4-5 have normal bleeding times. This made us question whether hemodialysis (HD) initiation was really necessary solely to improve platelet function. METHODS: In this prospective observational study, two 5 ml citrated blood samples and one 2 ml EDTA blood sample were collected from incident HD patients fulfilling inclusion criteria prior to HD initiation (baseline sample) and after three sessions of short duration, low flow, counter-current HD. In each instance, one sample was used to perform Collagen adenosine diphosphate closure time (CADPCT) using the Platelet function analyzer (PFA 200, normal range 68-142 seconds) and the second for light transmission aggregometry (LTA) with ADP as agonist (normal ≥50%). RESULTS: This study included 20 patients between October 2017 and February 2019. Overall, and in the subgroup with normal baseline CADPCT or LTA, there was no statistically significant improvement after HD. However, of the 30% of patients who had an abnormal baseline CADPCT, 50% attained a normal value after three HD sessions, and the overall reduction in CADPCT in this group was statistically significant (P = 0.02). Of those with a baseline normal CADPCT, 21% developed abnormal prolongation post HD. CONCLUSION: HD for the sole purpose of improving platelet function is only of benefit in the subgroup of patients with an abnormal CADPCT at baseline, with close to 50% normalizing their platelet function after three sessions of low flow, short duration, counter-current HD.

Safety and utility of kidney biopsy in patients with estimated glomerular filtration rate < 30 ml/min/1.73 m2.

AIM: Kidney biopsy (KBx) is the gold standard for evaluation of kidney disease, but is associated with a higher risk of complications in patients with reduced glomerular filtration rate (GFR). We studied the safety and utility of KBx in patients with eGFR <30 ml/min/1.73 m2 . METHODS: Consecutive adult patients with eGFR <30 ml/min/1.73 m2 , who were planned for a KBx and consented to participate were prospectively enrolled. Patients with solitary/transplant kidney or acute kidney injury were excluded. Haemoglobin was checked on the day of KBx and repeated 18-24 h later along with a screening ultrasound. Post-KBx complications were noted and their risk-factors analysed. The utility of the KBx was graded as effecting significant, some, or no change to subsequent management. RESULTS: Of the 126 patients included, 75% were male, 27.7% were diabetic, and the median eGFR was 13.5 ml/min/1.73m2 . Major complications occurred in 5.6%. Peri-renal haematomas were detected in 37.3%, and haematomas ≥2 cm were significantly more frequent in those with eGFR <15 ml/min/1.73 m2 (29.2% vs. 13%, p = .032). Dialysis was a risk factor, while pre KBx blood transfusion, diabetes and higher serum albumin were protective against any complication. KBx was more likely to make a significant difference in management in those with eGFR 15-29 ml/min/1.73m2 (44.1% vs. 11.1%, p < .001). Increasing age, lower serum creatinine and albumin were independently associated with KBx utility. CONCLUSION: KBx is relatively safe in severe kidney disease but its risk to benefit balance needs to be carefully considered when eGFR is <15 ml/min/1.73m2 .

Epidemiology, baseline characteristics and risk of progression in the first South-Asian prospective longitudinal observational IgA nephropathy cohort.

INTRODUCTION: Glomerular Research And Clinical Experiments-IgA Nephropathy in Indians (GRACE-IgANI) is the first prospective South Asian IgAN cohort with protocolized follow-up and extensive biosample collection. Here we report the baseline clinical, biochemical, and histopathologic characteristics of GRACE IgANI and calculate baseline risk of progression for the cohort. METHODS: 201 incident adults with kidney biopsy-proven primary IgAN were recruited into GRACE-IgANI between March 2015 and September 2017. As of April 30, 2020, the cohort had completed a median follow-up of 30 months (interquartile range [IQR] 16-39). RESULTS: The commonest clinical presentation in GRACE IgANI was hypertension, with or without proteinuria, and nephrotic-range proteinuria was present in 34%, despite <10 months of lead time to kidney biopsy. The GRACE-IgANI kidney biopsy data demonstrated a disproportionate absence of active glomerular lesions and overrepresentation of segmental sclerosing lesions and tubulointerstitial fibrosis at presentation, often coexistent with relatively well-preserved estimated glomerular filtration rate (eGFR) and low levels of proteinuria, especially in males. Baseline risk of progression was calculated for each evaluable patient using 2 different risk prediction tools. The median 5-year absolute risk of end-stage kidney disease (ESKD) was 19.8% (IQR 2.7-57.4) and median 5-year risk of progression to the combined endpoint of 50% decline in eGFR or ESKD was 35.5% using the 2 tools. CONCLUSIONS: The predicted risk of progression in this cohort was considerable. Over the next 5 years, we will dissect the pathogenic pathways that underlie this severe South Asian IgAN phenotype.

Post-transplant complications, patient, and graft survival in pediatric and adolescent kidney transplant recipients at a tropical tertiary care center across two immunosuppression eras.

BACKGROUND: We report pediatric PAKT patient and graft outcomes at a large tropical tertiary center spanning two transplant eras. METHODS: In this retrospective cohort study, all children ≤18 years who underwent kidney transplantation at our center between 1991 and 2016 were included. Data pertaining to their baseline characteristics, post-transplant events, and outcome were retrieved from transplant records and compared between transplant eras (1991-2005 and 2006-2016). RESULTS: A total of 139 children (mean age 15.2 ± 2.9 years) underwent PAKT during this period. The incidence of UTIs, CMV disease, BKVN, invasive fungal infections, new-onset diabetes after transplant, leucopenia, and recurrent NKD was higher in the 2006-2016 era (P < .001 for all), while 1-year cumulative BPAR was comparable (P = .100). Five-year graft and patient survival in the two eras were 89.9% and 94.2% (P = .365) and 92.1% and 95.3% (P = .739), respectively. Incidence of CMV disease, BKVN, graft loss, and death was lower in the calcineurin withdrawal group. Non-adherence accounted for 36% of graft loss; infections caused 43.7% of deaths. On multivariate Cox proportional hazards analysis, independent predictors for graft loss were UTIs and blood transfusion naïve status and for death were serious infections and glomerular NKD. CONCLUSIONS: PAKT in India has excellent long-term graft outcomes, though patient outcomes remain suboptimal owing to a high burden of infections. Current immunosuppression protocols need to be re-examined to balance infection risk, graft, and patient survival.

Catching the Worm Early: An Atypical Case of Bancroftian Filarial Nephropathy.

Filarial glomerular disease has been attributed to circulating immune complex deposition. We report here a rare manifestation of filarial nephropathy with microfilariae documented in glomerular capillaries in addition to immune complex glomerulonephritis, thus suggesting that direct toxicity may also contribute to the pathogenesis of this entity.

Protein complex prediction in interaction network based on network motif.

The enormous size of Protein-Protein Interaction (PPI) networks demands efficient computational methods to extract biologically significant protein complexes. A wide variety of algorithms have been proposed to predict protein complexes from PPI networks. However, it is still a challenging task to detect protein complexes with high accuracy and manageable sensitivity. In this manuscript, a novel complex prediction algorithm based on Network Motif (CPNM) is proposed. This algorithm addresses the role of proteins in the embeddings of network motif. These roles are used to define feature vectors and feature weights of proteins. Based on these features, a neighborhood search technique predict the protein complexes that consider both the inherent organization of proteins as well as the dense regions in PPI networks. The performance of the proposed algorithm is evaluated using various evaluation metrics like Precision, Recall, F-measure, Sensitivity, PPV, and Accuracy. The research finding indicates that the proposed algorithm outperforms most of the competing algorithms like MCODE, DPClus, RNSC, COACH, ClusterONE, CMC and PROCODE over the PPI network of Saccharomyces cerevisiae and Homo sapiens.

Review of tools and algorithms for network motif discovery in biological networks.

Network motifs are recurrent and over-represented patterns having biological relevance. This is one of the important local properties of biological networks. Network motif discovery finds important applications in many areas such as functional analysis of biological components, the validity of network composition, classification of networks, disease discovery, identification of unique subunits etc. The discovery of network motifs is a computationally challenging task due to the large size of real networks, and the exponential increase of search space with respect to network size and motif size. This problem also includes the subgraph isomorphism check, which is Nondeterministic Polynomial (NP)-complete. Several tools and algorithms have been designed in the last few years to address this problem with encouraging results. These tools and algorithms can be classified into various categories based on exact census, mapping, pattern growth, and so on. In this study, critical aspects of network motif discovery, design principles of background algorithms, and their functionality have been reviewed with their strengths and limitations. The performances of state-of-art algorithms are discussed in terms of runtime efficiency, scalability, and space requirement. The future scope, research direction, and challenges of the existing algorithms are presented at the end of the study.

Collagenofibrotic glomerulopathy - A rare disease diagnosed with the aid of transmission electron microscopy.

Collagenofibrotic glomerulopathy (CFG) is a rare idiopathic kidney disease characterized by abnormal deposition of atypical Type III collagen fibers in the glomerulus causing subendothelial and mesangial expansion, manifesting as progressive renal dysfunction accompanied by proteinuria. The majority of CFG cases reported in literature are from Japan where this disease entity was initially recognized. There is an increased awareness and diagnosis of this rare renal disease in India with the recent increase in utilization of electron microscopy (EM) in clinical diagnostic settings. We describe a 28-year-old Bangladeshi woman who presented with hypertension and nephrotic range proteinuria not amenable to treatment with steroids and cyclophosphamide, whose renal biopsy demonstrated diagnostic ultrastructural features of CFG. This illustrative case is presented to highlight the role of EM analysis for diagnostic accuracy in renal biopsy evaluation in addition to demonstrating the unusual renal biopsy findings of this rare entity.

Effects of Individualized Dialysate Sodium Prescription in Hemodialysis - Results from a Prospective Interventional Trial.

INTRODUCTION: Individualized dialysate sodium prescription does affect weight gain, blood pressure (BP), and intradialytic complications. A prospective interventional trial (Dialysate Individualised Sodium (DISO) trial) was conducted to study this issue in Indian patients. METHODS: Forty patients on thrice-weekly maintenance hemodialysis (HD) for at least 6 weeks were enrolled. The study was performed in two different phases. In the first phase, 12 consecutive HD sessions were done with a standard dialysate sodium concentration of 140 mEq/L. In the second phase, 12 consecutive HD sessions were done with dialysate sodium concentration set to individualized value (mean of pre-HD sodium concentration multiplied by Donnan coefficient of 0.95). Differences in pre- and post-HD sodium, interdialytic weight gain (IDWG), pre- and post-HD BP, thirst scores, and intradialytic adverse events during both phases were assessed. RESULTS: The mean age of patients was 45.65 years (24 males, 16 females). The mean serum pre-HD sodium level was 138.7 ± 1.7 meq/L in the standard phase and 138.2 ± 2.6meq/L in the individualized phase (P = 0.229). In the standard phase, the mean IDWG was 2.64 ± 1.56 kg and 2.13 ± 0.99 kg in the individualized phase (P = 0.008). The mean pre-HD systolic BP was 138 ± 18 mmHg and 134 ± 17 mmHg in the standard and individualized phases (P = 0.008). There was no difference in intradialytic symptoms, hypotensive episodes or requirement of interventions. Hypertension episodes occurred at a mean value of 2.2 and 1.2 in the standard and individualized phases, respectively (P = 0.010). CONCLUSION: The use of individualized dialysate sodium level is safe and results in lower IDWG, pre-HD systolic BP, and intradialytic hypertension in patients on HD.

TriRNSC: triclustering of gene expression microarray data using restricted neighbourhood search.

Computational analysis of microarray data is crucial for understanding the gene behaviours and deriving meaningful results. Clustering and biclustering of gene expression microarray data in the unsupervised domain are extremely important as their outcomes directly dominate healthcare research in many aspects. However, these approaches fail when the time factor is added as the third dimension to the microarray datasets. This three-dimensional data set can be analysed using triclustering that discovers similar gene sets that pursue identical behaviour under a subset of conditions at a specific time point. A novel triclustering algorithm (TriRNSC) is proposed in this manuscript to discover meaningful triclusters in gene expression profiles. TriRNSC is based on restricted neighbourhood search clustering (RNSC), a popular graph-based clustering approach considering the genes, the experimental conditions and the time points at an instance. The performance of the proposed algorithm is evaluated in terms of volume and some performance measures. Gene Ontology and KEGG pathway analysis are used to validate the TriRNSC results biologically. The efficiency of TriRNSC indicates its capability and reliability and also demonstrates its usability over other state-of-art schemes. The proposed framework initiates the application of the RNSC algorithm in the triclustering of gene expression profiles.

Fast and furious: a retrospective study of catheter-associated bloodstream infections with internal jugular nontunneled hemodialysis catheters at a tropical center.

BACKGROUND: Nontunneled hemodialysis catheters (NTHCs) remain the preferred vascular access at hemodialysis (HD) initiation in developing countries. We studied the incidence, risk factors and microbiological spectrum of jugular NTHC-associated bloodstream infections (CABSIs) at a tertiary care center in South Asia. METHODS: In this retrospective cohort study, all adult (≥18 years) incident patients who underwent jugular NTHC insertion for HD between January 2016 and June 2017, had no prior history of temporary vascular access insertion and were followed up for ≥14 days were included. RESULTS: A total of 897 patients underwent NTHC insertion during the study period and 169 patients fulfilled the inclusion criteria and contributed 7079 patient days of follow-up. CABSI incidence was 7.34 episodes per 1000 catheter days and median infection-free survival and time to CABSI were 96 and 24.5 days, respectively. In multivariate Cox regression analysis, immunosuppressive medication {hazard ratio [HR] 2.87 [95% confidence interval (CI) 1.09-7.55]; P = 0.033} and intravenous cefazolin use [HR 0.51 (95% CI 0.28-0.94); P = 0.031] was independently associated with CABSI. The cumulative hazard of CABSI was 8.3, 13.3, 17.6 and 20.9% at Weeks 1, 2, 3 and 4, respectively. Gram-negative organisms were the most common etiological agents (54.7%) and 40.3% of CABSIs were caused by drug-resistant organisms. Gram-negative and Gram-positive CABSIs were associated with neutrophil left shift and higher procalcitonin compared with coagulase-negative staphylococcal CABSIs. CONCLUSION: In South Asia, NTHC-associated CABSIs occur early and are predominantly Gram negative. We hypothesize that poor hygiene practices may play a role in this phenomenon.

Disjoint motif discovery in biological network using pattern join method.

The biological network plays a key role in protein function annotation, protein superfamily classification, disease diagnosis, etc. These networks exhibit global properties like small-world property, power-law degree distribution, hierarchical modularity, robustness, etc. Along with these, the biological network also possesses some local properties like clustering and network motif. Network motifs are recurrent and statistically over-represented subgraphs in a target network. Operation of a biological network is controlled by these motifs, and they are responsible for many biological applications. Discovery of network motifs is a computationally hard problem and involves a subgraph isomorphism check which is NP-complete. In recent years, researchers have developed various tools and algorithms to detect network motifs efficiently. However, it is still a challenging task to discover the network motif within a practical time bound for the large motif. In this study, an efficient pattern-join based algorithm is proposed to discover network motif in biological networks. The performance of the proposed algorithm is evaluated on the transcription regulatory network of Escherichia coli and the protein interaction network of Saccharomyces cerevisiae. The running time of the proposed algorithm outperforms most of the existing algorithms to discover large motifs.

Application of dynamic expansion tree for finding large network motifs in biological networks.

Network motifs play an important role in the structural analysis of biological networks. Identification of such network motifs leads to many important applications such as understanding the modularity and the large-scale structure of biological networks, classification of networks into super-families, and protein function annotation. However, identification of large network motifs is a challenging task as it involves the graph isomorphism problem. Although this problem has been studied extensively in the literature using different computational approaches, still there is a lot of scope for improvement. Motivated by the challenges involved in this field, an efficient and scalable network motif finding algorithm using a dynamic expansion tree is proposed. The novelty of the proposed algorithm is that it avoids computationally expensive graph isomorphism tests and overcomes the space limitation of the static expansion tree (SET) which makes it enable to find large motifs. In this algorithm, the embeddings corresponding to a child node of the expansion tree are obtained from the embeddings of a parent node, either by adding a vertex or by adding an edge. This process does not involve any graph isomorphism check. The time complexity of vertex addition and edge addition are O(n) and O(1), respectively. The growth of a dynamic expansion tree (DET) depends on the availability of patterns in the target network. Pruning of branches in the DET significantly reduces the space requirement of the SET. The proposed algorithm has been tested on a protein-protein interaction network obtained from the MINT database. The proposed algorithm is able to identify large network motifs faster than most of the existing motif finding algorithms.

The long-term impact of hepatitis C infection in kidney transplantation in the pre-direct acting antiviral era.

Hepatitis C virus (HCV) infection in kidney transplantation is an important issue with effects on patient and graft survival. The current standard of care involves using oral Direct Acting Antiviral drugs. Till recently, pre-transplant treatment with interferon was the only option for treatment. We studied 677 consecutive kidney transplant recipients with HCV infection. 5.2% patients had evidence of HCV infection. 2.0% were newly detected to have HCV infection after transplant (de novo HCV group). Nearly 28.6% had negative antibody tests but positive Nucleic Acid Test at the time of diagnosis. Eighty-five percent of pre-transplant HCV-positive patients were treated with interferon-based regimens. Early virologic response was seen in 66.6%. End of treatment response was achieved by 94.1%. Sustained virologic response was seen in 81.2%. Overall, patient and graft survival were not different between HCV and control groups (log-rank P = 0.154). Comparing HCV and control groups, there was a tendency toward increased fungal (11.4% vs. 5.6%, P = 0.144) and CMV infections (25.7% vs. 17.1%, P = 0.191) in the HCV group, though it did not reach statistical significance. Eighty-percent of the interferon-treated patients suffered side effects. On comparing, the pre-transplant HCV-positive group (85% treated) with the de novo HCV group (none treated), the de novo group had significantly reduced patient survival (P = 0.020) and NODAT (35.7 vs 4.8%, P = 0.028), and a tendency toward higher CMV infections (35.7% vs 19%, P = 0.432). In addition, death and hepatic complications (decompensated liver disease, fibrosing cholestatic hepatitis) occurred only in de novo HCV group. These results highlight the need for continued post-transplant treatment of HCV positive patients. The newer anti-HCV drugs are expected to fulfill this felt-need in kidney transplantation but long-term results are awaited. This study can serve as a benchmark for future studies to compare the long-term effect of Direct Acting Antiviral drugs.

Motif discovery in biological network using expansion tree.

Networks are powerful representation of topological features in biological systems like protein interaction and gene regulation. In order to understand the design principles of such complex networks, the concept of network motifs emerged. Network motifs are recurrent patterns with statistical significance that can be seen as basic building blocks of complex networks. Identification of network motifs leads to many important applications, such as understanding the modularity and the large-scale structure of biological networks, classification of networks into super-families, protein function annotation, etc. However, identification of network motifs is challenging as it involves graph isomorphism which is computationally hard. Though this problem has been studied extensively in the literature using different computational approaches, we are far from satisfactory results. Motivated by the challenges involved in this field, an efficient and scalable network Motif Discovery algorithm based on Expansion Tree (MODET) is proposed. Pattern growth approach is used in this proposed motif-centric algorithm. Each node of the expansion tree represents a non-isomorphic pattern. The embeddings corresponding to a child node of the expansion tree are obtained from the embeddings of the parent node through vertex addition and edge addition. Further, the proposed algorithm does not involve any graph isomorphism check and the time complexities of these processes are O(n) and O(1) , respectively. The proposed algorithm has been tested on Protein-Protein Interaction (PPI) network obtained from the MINT database. The computational efficiency of the proposed algorithm outperforms most of the existing network motif discovery algorithms.

Protocol and rationale for the first South Asian 5-year prospective longitudinal observational cohort study and biomarker evaluation investigating the clinical course and risk profile of IgA nephropathy: GRACE IgANI cohort.

Background: IgA nephropathy (IgAN) is the most common primary glomerulonephritis and an important cause of end-stage kidney disease. Unlike the slowly progressive course seen among Caucasian and East Asian subjects (actuarial survival 80-85% over 10 years), in India about 30-40% of patients have nephrotic syndrome and renal dysfunction at presentation and a 10-year renal survival of 35%, as reported from a retrospective registry. These observations cannot be entirely attributed to a lack of uniform screening protocols or late referral and attest to the probability that IgAN may not be the same disease in different parts of the world. Methods: We will prospectively recruit 200 patients with IgAN (the GRACE IgANI- Glomerular Research And Clinical Experiments- Ig A Nephropathy in Indians-cohort) and stratify them into low and high risk of progression based on published absolute renal risk scores. We will test the validity of this risk score in an unselected Indian IgAN population over a 5-year follow-up period. In parallel, we will undertake extensive exploratory serum, urine, renal and microbiome biomarker studies, firstly, to determine if the underlying pathogenic pathways are the same in Indian IgAN compared to those reported in Caucasian and East Asian IgAN. Secondly, we will systematically assess the value of measuring selected biomarkers and adding this data to traditional measures of risk in IgAN to predict kidney failure. We ultimately hope to generate a composite IgAN risk score specific for the Indian population. Ethics and data dissemination: Approval was obtained from the Institutional Review Board (Silver, Research and Ethics Committee) of the Christian Medical College, Vellore, India (Ref. No. IRB Min. No. 8962 [Other] dated 23.07.2014 and IRB Min. No. 9481 [Other] dated 24.06.2015). It is anticipated that results of this study will be presented at national and international meetings, with reports being published from late 2018.

Podocyte Infolding Glomerulopathy (PIG) in a Patient With Undifferentiated Connective Tissue Disease: A Case Report.

Podocyte infolding glomerulopathy (PIG) is a recently described pathologic entity characterized by diffuse podocyte infolding into the glomerular basement membrane (GBM) associated with ultrastructurally demonstrable microspherular aggregates. The clinical features, significance, and pathogenesis of this condition are still not well delineated because only a few cases have been documented to date, all from Japan. We report a case of PIG associated with undifferentiated connective tissue disease in an Indian woman who presented with nephrotic syndrome while undergoing treatment for an autoimmune disorder. Ultrastructural analysis of the kidney biopsy specimen revealed unusual subepithelial aggregates of microspherules admixed with few microtubules alongside extensive infolding of podocyte foot processes into the underlying GBMs. Characteristic clustering of these microparticles near the invaginated tips of podocyte foot processes in the GBM was observed on transmission electron microscopy. The patient's clinical condition responded favorably to immunosuppressive therapy. The clinical, light microscopic, and diagnostic electron microscopic features of this condition are highlighted in this report in an attempt to contribute some insights into the possible pathogenetic mechanisms of this obscure entity.