Continuing arteriovenous fistula creation by nephrologist and its outcome during COVID pandemic-Analysis of 376 cases.

There has been a significant reduction of elective surgeries including creation of arteriovenous fistulas (AVF) during the ongoing pandemic by the surgeons. Here, we report the retrospective observational data of AVF creation by nephrologists in a single center, during a period of 8 months. A total of 376 fistulae were created in 310 patients. Patients were followed up at 2, 6, and 12 weeks. Twenty-eight patients required fistula creation twice, 16 patients thrice, and two patients underwent fistula creation four times. Of the total, 259 (68.8%) fistulae were radio-cephalic while 99 (26.3%) and 18 (4.79%) were brachio-cephalic and brachio-basilic, respectively. A total of 207 (67%) patients were already on hemodialysis whereas 103 (33%) were planned for elective initiation after fistula maturation. Of the 211 (69%) patients who completed 3 months of follow-up, 31 (15%) expired and 7 (3.3%) were lost to follow-up. Primary failure was observed in 70 (33.2%) fistulae. Fifteen (7.1%) patients were noted to be COVID positive during the follow-up. A total of 279 (90%) patients were alive at last follow-up. Amongst 20 dialysis staffs with 10 nephrologists, only two have developed COVID. Both were having mild illness and recovered completely. This study demonstrates that AVF creation can be performed safely with careful screening and by using adequate personal protective equipment.

Comparative diagnostic utility of different urinary biomarkers during pre-albuminuric stages of non-hypertensive type 2 diabetic nephropathy.

Background & objectives: Activation of renin-angiotensin system and tubulointerstitial damage might be seen in pre-albuminuria stage of diabetic nephropathy (DN). Here, diagnostic utility of four urinary biomarkers [Angiotensinogen (Angio), Interleukin (IL)-18, Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Cystatin] during pre-albuminuria stages of non-hypertensive type 2 diabetes patients was studied. Methods: A total of 952 type 2 diabetes mellitus (T2DM) patients were screened for nephropathy [estimated glomerular filtration rate (eGFR) ≥120 ml/min and albumin-creatinine ratio (ACR) ≥30], and 120 patients were followed up for one year. At one year, they were classified into hyperfiltration (43), normoalbuminuria (29) and microalbuminuria (48) groups. Another 63 T2DM patients without nephropathy were included as controls. Hypertension, patients on angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, eGFR <60 ml/min/1.73 m2 and all proteinuric conditions were excluded. All were subjected to testing for urine protein, ACR, HbA1C, eGFR, along with urinary biomarkers (IL-18, cystatin-C, NGAL and AGT). Comparative analysis of all the diagnostic tests among different subgroups, correlation and logistic regression was done. Results: Urinary IL-18/Cr, cystatin/creatinine (Cr) and AGT/Cr levels were higher in groups of hyperfiltration (13.47, 12.11 and 8.43 mg/g), normoalbuminuria (9.24, 11.74 and 9.15 mg/g) and microalbuminuria (11.59, 14.48 and 10.24 mg/g) than controls (7.38, 8.39 and 1.26 mg/g), but NGAL/Cr was comparable. The area under receiver operating characteristic curve (AUC) and sensitivity of AGT to detect early CKD were higher than ACR and eGFR (0.91 and 90.4%, 0.6 and 40% and 0.6 and 37%, respectively). AUC values of other biomarkers, namely IL-18/Cr, cystatin/Cr and NGAL/Cr, were 0.65, 0.64 and 0.51, respectively. Angio/Cr and IL-18/Cr showed correlation with log albuminuria (r=0.3, P=0.00, and r=0.28, P=0.00, respectively). NGAL showed correlation with log eGFR (r=0.28 P=0.00). Multivariate logistic analysis showed that odds ratio of developing nephropathy was 7.5 times with higher values of log Angio/Cr. Interpretation & conclusions: Urinary AGT showed a higher diagnostic value than ACR and eGFR followed by IL-18 and cystatin to diagnose DN during pre-albuminuric stages.

Novel urinary biomarkers in pre-diabetic nephropathy.

BACKGROUND: Renal involvement was thought to occur more than 10 years after onset of diabetes, but recent studies provide evidence that it starts even in the pre-diabetes stage. However, there is no sensitive marker to detect these changes at such early stages. Novel urinary biomarkers have showed promising results in detection of early nephropathy in pre-diabetics. METHODS: A total of 91 subjects (diabetes 61 and pre-diabetes 30) were enrolled into the study. Urinary biomarkers such as urine Neutrophil Gelatinase-Associated Lipocalin (NGAL), urine Cystatin C and urine albumin-creatinine ratio (UACR) were estimated. Subjects were further divided in four groups on the basis of UACR: pre-diabetes with normoalbuminuria (21); pre-diabetes with microalbuminuria (9); diabetes with normoalbuminuria (37); and diabetes with microalbuminuria (24). The relationship of UACR, NGAL, and Cystatin C was estimated. RESULTS: Urine levels of NGAL and Cystatin C were significantly higher in microalbuminuria group compared to normoalbuminuria. UACR was positively correlated to urine NGAL-creatinine ratio (UNCR) and urine Cystatin C-creatinine ratio (UCCR) in both diabetes and pre-diabetes. On logistic regression odds ratio of UNCR to predict microalbuminuria in diabetes and pre-diabetes was 1.070 (p = 0.000) and 1.138 (p = 0.010), respectively. Area under curve was determined by ROC analysis, and UNCR was found to be better than UCCR for estimating microalbuminuria. CONCLUSION: Tubular damage may play major role in development of nephropathy in pre-diabetes. Newer markers like urine NGAL and Cystatin C are raised early in diabetes and pre-diabetes nephropathy.

Study on prediction of arterio-venous fistula maturation by flow mediated dilatation and AVF blood flow.

BACKGROUND: The physiology and pathology of AVF maturation depends on the vessels characteristics and its ability to remodel. Outcome of AVF using flow mediated dilatation (FMD), AVF blood flow and diameter has been studied. METHODOLOGY: Present observational study included single stage AVF (both Radiocephalic and Brachiocephalic) in consecutive CKD five patients (n = 158) prospectively over 1 year. Demographic and Doppler ultrasound parameters of upper limb (for vessel diameter and FMD) at baseline were recorded. Blood flow, diameter and depth of AVF were studied at 2, 6 and 12 weeks and their association with clinical maturation (usage of fistula with two needles for 75% of dialysis sessions during 15 day period) was studied (n = 129, after excluding lost to followup and expired patients; accordingly cohort was divided in matured (M) or non-matured (NM) groups. Clinical and radiological parameters between both groups were compared; receiver operator curve (ROC) and correlation of Doppler parameters were analysed. RESULTS: Of 129 AVF, 67.4% were matured and 32.5% non-matured. Mean age was 40 years with male predominance75% in both the groups. The mean arterial diameter for distal (NM = 1.96 ± 0.58 and M = 2.02 ± 0.41) and proximal AVF (NM = 3.37 ± 0.82 and M = 3.36 ± 0.75) was not statistically different in both the groups. The matured fistula group had a mean FMD of 11.67 ± 4.09 as against FMD value of 9.365 ± 3.55 in the failed fistula group (p value 0.01). For maturation prediction, sensitivity and specificity of blood flow at 2 weeks were 86.2% and 59.5% and at 6 weeks 96.6% and 64.3%, respectively. In multivariate analysis predictors for AVF maturation were FMD (adjusted odds ratio (AOR) = 1.15) and blood flow (AOR = 1.67). CONCLUSION: Second and Sixth week AVF blood flow was found to be predicting AVF maturation. Higher baseline FMD correlated with the AVF maturation, but not with vessel diameter.

Comparison of clinical examination, doppler and fistulogram for arterio-venous fistula surveillance in detecting secondary failure.

BACKGROUND: Arteriovenous Fistula (AVF) surveillance is required to detect early dysfunction (thrombosis, stenosis) and its timely correction prolongs access-patency. Clinical examination (CE) and doppler have been used as screening/surveillance of AVF, for early detection of AVF dysfunction. Since there was inadequate evidence for KDOQI to make recommendations on AVF surveillance and on secondary failure rate. We compared CE, doppler and fistulogram as surveillance modalities in detecting a secondary failure in matured AVF. METHODOLOGY: This prospective-observational, single-center study, was done between December 2019-April 2021. CKD stage 5 patients on dialysis/Not-on-dialysis with matured AVF were included at third month. CE, doppler (blood flow, vein diameter, depth), and fistulogram were done at third and sixth month. Secondary failure was assessed at sixth month classifying AVF to patent/functional and failed group. Diagnostic tests were performed by comparing three methods considering fistulogram as gold-standard. Residual urine output is also monitored to look for any contrast induced residual renal function loss. RESULTS: Of total 407 created AVF, 98 (24%) had primary failure. Twenty-five (6%) had surgical complications including unsuccessful AVF and aneurysm/rupture, 156 lost follow-up at third month, 104 consented patients were enrolled, 16 lost to follow-up subsequently, and 88 patients' data were analyzed at the end. At the sixth month, 76(86.4%) had patent AVF, 8 (9.1%) had secondary failure (Thrombosis-4, Central Venous Stenosis-4), and 4 (4.1%) patients expired. Considering fistulogram as a diagnostic standard, CE showed 87.5% sensitivity, and 93.4% specificity (cohen's kappa value of 0.66). Doppler had sensitivity and specificity of 87% and 96% respectively (cohen's kappa value of 0.75), Combination of clinical examination with doppler showed sensitivity and specificity of 100% and 89% respectively. CONCLUSION: Although the secondary AVF failure rate is less than the primary, CE is an important and valuable tool in the diagnosis and surveillance of AVF in detecting its dysfunction. Moreover, CE with doppler can be used as a surveillance protocol that can detect early AVF dysfunction at par with Fistulogram.

An Unusual Case of High-Grade Non-Hodgkin Lymphoma Masquerading as Acute Pyelonephritis with Acute Kidney Injury.

Renal involvement in non-Hodgkin lymphoma (NHL) has myriad of morphological features. We discuss an unusual case who presented as acute pyelonephritis (leucocytosis and acute kidney injury), ovarian mass and compressive myelopathy finally diagnosed as Non Hodgkins Lymphoma.

Single-center Haemodialysis Experience in India During COVID-19.

Introduction: Since COVID-19 has been announced as a pandemic, outcome of dialysis patients in terms of morbidity and mortality from India is lacking. We studied the clinical, epidemiological features of COVID-19 along with outcome in terms of mortality in our dialysis cohort. Methods: Data of End-Stage Kidney Disease (ESKD) patients who were admitted in COVID-19 designated hospital block as positive and suspected patients from 1st April 2020 to 31st July 2020 was retrieved. Data about epidemiological characteristics, clinical features, mortality outcomes of COVID-19 positive and negative patients were analyzed. Results: A total of 97 ESKD patients were admitted during the study period, of which 44 (45.4%) and 53 (54.6%) patients were found to be COVID-19 positive and negative respectively. The mean age of COVID positive patients was 46 years with 54.5% being female. Only three patients (6.8%) remained asymptomatic throughout the course of illness. Amongst COVID-19 positive, 20 (45.45%) were severely ill while 18 (40.9%) were having mild illnesses. Breathlessness (65.9%) and fever (61.4%) were common symptoms. The death occurred in 17 (38.6%) and 25 (47.1%) COVID-19 positive and negative ESKD patients respectively. 14 (82.3%) patients who expired amongst COVID-19 positive were having severe illness and significantly more were associated with negligible residual renal function. Conclusions: Breathlessness and fever were common symptoms amongst COVID-19 ESKD patients. Very few patients remained asymptomatic in our cohort and significantly more mortality is observed in severely ill patients and those with negligible residual renal function.

Ultra-low CONtraSt PCI vs conVEntional PCI in patients of ACS with increased risk of CI-AKI (CONSaVE-AKI).

OBJECTIVES: This prospective, randomized study assessed short-term outcomes and safety of ultra-low contrast percutaneous coronary intervention(ULC-PCI) vs conventional PCI in high risk for contrast induced acute kidney injury(CI-AKI) patients presenting with acute coronary syndrome(ACS). BACKGROUND: Patients at an increased risk of developing CI-AKI can be identified prior to PCI based on their pre-procedural risk scores. ULC-PCI is a novel contrast conservation strategy in such high risk patients for prevention of CI-AKI. METHODS: 82 patients undergoing PCI for ACS were enrolled having estimated glomerular filtration rate(eGFR) < 60 ml/min/1.73 m2 and moderate to very high pre-procedural risk of developing CI-AKI as calculated by Maioli risk calculator. They were randomized into two groups of 41 patients each of ULC-PCI (contrast volume ≤ patient's eGFR) and conventional PCI (contrast volume ≤ 3xpatient's eGFR). Primary end point was development of CI-AKI. RESULTS: Baseline clinical and angiographic characteristics were similar between groups. Primary outcome of CI-AKI occurred more in patients of the conventional PCI group [7 (17.1%)] than in the ULC PCI group [(0 patients), p = 0.012]. Contrast volume (41.02 (±9.8) ml vs 112.54 (±25.18) ml; P < 0.0001) was markedly lower in the ULC-PCI group. No significant difference in secondary safety outcomes between two study arms at 30 days. IVUS was used in 17% patients in ULC PCI. CONCLUSION: ULC-PCI in patients with increased risk of developing CI-AKI is feasible, appears safe, and has the potential to decrease the incidence of CI-AKI specially in resource limited setting such as ours where coronary imaging by IVUS is not possible in every patient.

Longitudinal Study to Find the Association of Serum Phosphorus Level with FGF23 in Three Different Hyperphosphatemia Management Groups of Stage 3 and 4 Chronic Kidney Disease (CKD) Patients.

Background: There is paucity of clinical evidence on target serum phosphorus levels in early chronic kidney disease (CKD). Present longitudinal study was done to find target phosphorus level and its association with fibroblast growth factor (FGF23) in three different hyperphosphatemia management groups. Methods: This 1-year, prospective, randomized controlled, open-labelled study was conducted among three equally allocated treatment groups that consisted of 120 screened early CKD patients totally. Group 1 patients were given dietary phosphorus modification (n = 40), group 2 patients were administered calcium-based phosphate binders (n = 40), and group 3 patients were given non-calcium-based phosphate binders (n = 40). Three-monthly dietary assessment, MDRD estimated glomerular filtration rate (eGFR), phosphorus, calcium, iPTH, alkaline phosphatase, and six-monthly FGF23, 2D echocardiography, and X-ray of chest and abdomen were performed. Association of three categories of phosphorus level up to 3.9, 4-5, and >5mg/dl, rate of progression of all parameters, and correlation with FGF23 were studied among all three groups. Results: At baseline, all clinical and biochemical parameters were equally distributed with a controlled nutritional phosphate among all groups. There was no significant difference of FGF23 levels from all the three categories of phosphorus level among all groups. Serum phosphorus at the level of 5 mg/dl was associated with iPTH and eGFR at 1 year. Over 1 year, there was a significant decline in serum phosphorus levels in group 1 (P 0.02), group 2 (P 0.00), and group 3 (P 0.05). FGF23 declined significantly only in group 3 (P 0.00). There was no correlation of FGF23 with serum phosphorus levels (P 0.13). However, FGF23 correlated positively with iPTH (P 0.03, r = 0.19). Conclusion: Serum phosphorus levels upto 5mg/dl had no effect on FGF23 at early CKD stages. Although different treatment groups showed significant phosphorus reduction, non-calcium phosphate binder had a major impact on FGF23 reduction.

Effect of Vitamin D on Urinary Angiotensinogen Level in Early Diabetic Nephropathy.

BACKGROUND: Urinary angiotensinogen (UAGT) is supposed to be a marker of activation of the intrarenal renin- angiotensin system (RAS) system in early diabetic nnephropathy (EDN). Vitamin D has been studied as a negative regulator of the circulating and tissue RAS activity, so its supplementation may prevent the progression of diabetic nephropathy (DN). This study was planned to assess the RAS activation and effect of vitamin D supplementation in EDN progression by estimating the UAGT level. METHODS: A total of 103 EDN subjects were randomized in two groups to receive either cholecalciferol (54) or matching placebo (49) in a double-blind manner. All were subjected to routine investigations, urinary albumin-to-creatinine ratio (UACR), UAGT, vitamin D, and intact parathyroid hormone (iPTH) at the 0 and 6 months. A total 40 healthy controls were also included for assessment of the same investigations at 0 month. RESULTS: Significant reduction of UACR, UAGT, and iPTH level were corroborated with an increase in 25(OH) vitamin D level from 0 to 6 months (all four P < 0.001). After 6 months, the median [interquartile range (IQR)] of UAGT and UACR levels was significantly lower in the cholecalciferol group as compared to placebo group (p < 0.001 and P = 0.04, respectively). The median UAGT level was significantly higher in patients with EDN (cholecalciferol & placebo Group) than control group at 0 month (p = 0.001). CONCLUSION: Significantly higher UAGT levels in EDN supports the role of intrarenal RAS activation. A significant decrease in UAGT level in the cholecalciferol group supports the beneficial role of vitamin D supplementation in the progression of EDN.

Comparative evaluation of immunoperoxidase versus immunofluorescent techniques in interpretation of kidney biopsies.

BACKGROUND: Immunofluorescence (IF) on frozen sections has been considered to be the gold standard for evaluation of kidney biopsy specimens. Immunohistochemistry (IHC) method can also be used for this purpose with advantages of being applicable on paraffin embedded tissue, providing permanent sections, and not requiring a specialized microscope for interpretation. Our aim was to evaluate IHC as an alternative to IF in the diagnostic assessment of kidney biopsy specimens. METHODS: One hundred kidney biopsy specimens were subjected to both IF and IHC staining for immunoglobulins (Ig), IgG, IgA, IgM and complement components c3 and c1q. IF staining was done on frozen sections. IHC staining was performed on paraffin-embedded tissue following proteolytic antigen retrieval. The sections were evaluated, and the results of IHC were compared with IF. RESULTS: Concordant observations were 98%, 87%, 89%, 83%, and 89% for IgA, IgM, IgG, C3 and C1q, respectively. The sensitivity of IHC method for Igs was found to be high (92%, 86.5%, and 95.1%, respectively for IgA, IgM, and IgG). 91% cases showed concordance of the intensity of the deposits while 100% cases showed a concordance of the pattern. Statistically, there was no significant difference in outcomes between IF and IHC for IgA, IgM, and IgG. However, statistically significant difference was found in the results for complement proteins. CONCLUSION: In this study, it is documented that IHC is, with few exceptions, equal to IF for the detection of Igs. Standardized immunoperoxidase method on the paraffin embedded, formalin fixed needle kidney biopsies could successfully replace the IF method in the diagnosis of glomerulonephritis.

Evaluation of Protein-Energy Wasting and Inflammation on Patients Undergoing Continuous Ambulatory Peritoneal Dialysis and its Correlations.

BACKGROUND: Protein-energy wasting (PEW) and heightened inflammation are prevalent in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) and is a strong risk factor for morbidity and mortality in these patients. Evaluation of PEW, prevalence of inflammation as well as interrelationship between various nutritional indices and inflammation has not been studied in much detail in patients undergoing CAPD. OBJECTIVES: This study was conducted to evaluate the interrelationship between PEW and inflammation in patients undergoing CAPD. PATIENTS AND METHODS: Sixty-three patients undergoing CAPD (M = 28, F = 35) were assessed with regard to their nutritional status and inflammation after a minimum of 3 months CAPD initiation. Nutritional status was assessed by dietary diary, anthropometry, subjective global assessment, and multifrequency bioelectrical impedance analysis (BIA). In addition, their serum albumin, prealbumin, transferrin, and cholesterol level were measured. Also, inflammation in these patients was assessed by High-Sensitivity C-Reactive Protein (hs-CRP > 3 mg/L) and Interleukin-6 (IL-6 > 2 µg/mL). Later on, diagnosis of malnutrition was made based on different methods. Correlation between inflammation and various nutritional assessment indices were analyzed statistically. RESULTS: Mean (SD) age of the patients was 57.6 (11.6) years. The average (SD) calorie and protein intake per day were 25.5 (4.6) kcal and 0.81 (0.2) mg, respectively. The mean and standard deviation of anthropometry variables of body mass index (BMI), mid-arm circumference (MAC), tricipital skin-fold thickness (TST), mid-arm muscle circumference (MAMC), and corrected mid-arm muscle area (cMAMA) were 23.7 ± 5 kg/m(2), 26.3 ± 4.5 cm, 1.624 ± 0.4 cm, 25.6 ± 4.5 cm, and 45.7 ± 19.7 cm(2), respectively. The mean values of serum protein, albumin, prealbumin, transferrin, cholesterol, triglyceride, hs-CRP, and IL-6 were 5.9 g/dL, 3.0 g/dL, 21.11 mg/dL, 130.6 mg/dL, 155.9 mg/dL, 136.1 mg/dL, 8.8 ± 7.6 mg/L, and 8.4 ± 12.2 µg/dL, respectively. Based on subjective global assessment (SGA); 11.63 (17.4%), 34.63 (54%), and 18.65 (28.6%) patients undergoing CAPD had normal, moderate, and severe malnutrition status, respectively. According to serum albumin level; 13.63 (21%), 39.63 (62%), and 11.63 (17%) patients undergoing CAPD had normal, moderate, and severe malnutrition status, respectively. Finally, based on BMI; 33.63 (52%), 23.63 (37%), and 7.63 (11%) patients undergoing CAPD had normal, moderate, and severe malnutrition status, respectively. About 76.1% and 9.5% of patients undergoing CAPD were malnourished based on lean tissue index (LTI) and fat tissue index (FTI), respectively. Based on hs-CRP and IL-6 findings, 70% (44/63) and 71.8% (45/63) of patients undergoing CAPD had high inflammation, respectively. High sensitive C-reactive protein correlated negatively (significantly) with serum albumin, prealbumin, and transferrin. Interleukin -6 correlated negatively (significantly) with MAC; MAMA; serum albumin, cholesterol, and transferrin. There was significant positive correlation between hs-CRP and IL-6. There is statistically significant difference in total protein intake (g/d), protein intake (g/kg/d), serum protein (g/dL), albumin (g/dL), transferrin (mg/dL), and cholesterol (mg/dL) between patients with and without inflammation. CONCLUSIONS: Protein-energy wasting (80% - 85%) by various methods and inflammation (70%) was very prevalent among patients undergoing CAPD. Inflammatory markers show significant negative correlation with anthropometry and serological markers. Inflammatory markers are suggested to be included in the regular assessment of patients undergoing CAPD, for the better management of protein-energy wasting.