Determinants of non-diabetic kidney diseases in type 2 diabetic patients: Twenty years of single center experience.

BACKGROUND: Diabetic nephropathy is one of the most common complications associated with diabetes. However, non-diabetic kidney disease has been reported in patients with type 2 diabetes at varying incidence rates. The objective of our study is to investigate the occurrence, clinicopathological characteristics, and inflammatory markers linked to diabetic and non-diabetic nephropathy (NDN) in patients with type 2 diabetes mellitus (DM). Additionally, we aimed to explore the possibility of identifying non-diabetic pathology using different biopsy indications. MATERIALS AND METHODS: A total of 159 patients with type 2 DM who underwent renal biopsy at a tertiary care nephrology clinic between January 2000 and January 2022 were enrolled in the study. We collected comprehensive data, including patient demographics, co-morbidities, diabetes duration, renal biopsy indications and results, serological markers, renal function, diabetic retinopathy (DRP), full blood count, blood biochemistry, urinalysis, and inflammatory markers. Patients were categorized based on their biopsy indications, and their biopsy results were classified into three groups: isolated NDN, isolated diabetic nephropathy (DN), and mixed nephropathy with concurrent NDN. We evaluated the relationship between biopsy indications and accompanying pathologies and statistically assessed the likelihood of each biopsy indication detecting non-diabetic renal pathology. Additionally, differences in other data, including demographic and laboratory results and medical histories, among the three groups were investigated. RESULTS: The most frequent indication of renal biopsy was atypical presentations of nephrotic syndrome or nephrotic range proteinuria (ANS/ANP) in 25.1% of patients. Other indications included unexplained renal failure (URF) in 22.6%, atypical presentations of non-nephrotic range proteinuria (ANNP) in 18.2%, acute kidney injury or rapidly progressive kidney dysfunction (AKI/RPKD) in 16.9%, microscopic hematuria in 15.7%, URF with ANNP in 11.3%, and severe nephrotic range proteinuria (SNP) in 9.4%. Renal biopsy revealed isolated NDN in 64.8%, DN in 25.1%, and mixed nephropathy in 10.1% of patients. Primary glomerular diseases were the main non-diabetic renal pathology, predominantly focal segmental glomerulosclerosis (FSGS) (36.4%) followed by MN (10.6%) and IgA nephropathy (7.5%). In comparison with the isolated DN and mixed nephropathy groups, patients in the isolated NDN group had significantly shorter diabetes duration, fewer DRP, as well as lower serum creatinine and neutrophil-to-lymphocyte ratio (NLR). Multivariate logistic regression analysis revealed that presence of hematuria (OR 4.40; 95% CI 1.34 - 14.46, p = 0.014), acute nephrotic range proteinuria (OR 11.93; 95% CI 1.56 - 90.77, p = 0.017), and AKI/APKD (OR 41.08; 95% CI 3.40 - 495.39, p = 0.003) were strong predictors of NDN. Lower NLR (OR 0.77; 95% CI 0.60 - 0.98, p = 0.035), shorter duration of diabetes (OR 0.90; 95% CI 0.84 - 0.97, p = 0.010), and absence of DRP (OR 0.35; 95% CI 0.12 - 0.98, p = 0.046) were also found to be independent indicators of NDN. Receiver operating characteristic curve (ROC) analysis revealed a cut-off value of ≤ 3.01 for NLR (sensitivity of 63.1%, specificity of 63.5%) with regards to predicting non-diabetic renal pathology (p = 0.006). CONCLUSION: Renal biopsy findings in patients with type 2 DM highlight that the prevalence of NDN may be higher than assumed, as presented mainly in the form of primary glomerular disease. The presence of AKI/RPKD, hematuria, and ANS/ANP serves as a reliable indicator of non-diabetic renal pathology. In more ambiguous situations, factors such as a shorter duration of diabetes, absence of DRP, and a lower NLR value may assist clinicians in biopsy decision.

Unexpectedly High Prevalence of Low Alpha-Galactosidase A Enzyme Activity in Patients with Focal Segmental Glomerulosclerosis

OBJECTIVES: Fabry disease (FD) is a rare disease associated with sphingolipid accumulation. Sphingolipids are components of plasma membranes that are important in podocyte function and accumulate in various glomerular diseases such as focal segmental glomerulosclerosis (FSGS). Both FD and FSGS can cause podocyte damage and are classified as podocytopathies. In this respect, FD and FSGS share the same pathophysiologic pathways. Previous screening studies have shown that a significant proportion of end-stage renal disease (ESRD) patients receiving hemodialysis (HD) have unsuspected FD, and the prevalence of low alpha-galactosidase A (αGLA) enzyme activity in these patients is higher than that in the normal population. We aimed to compare αGLA enzyme activity in patients with biopsy-proven FSGS and ESRD receiving HD. METHODS: The records of 232 patients [62 FSGS (F/M: 33/29); 170 HD (M/F: 93/79)] were evaluated retrospectively. The screening was performed based on the αGLA enzyme activity on a dried blood spot, with the confirmation of plasma LysoGb3 levels, and the known GLA mutations were tested in patients with low enzyme activities. The two groups were compared using these parameters. RESULTS: The mean level of αGLA enzyme activity was found to be lower in FSGS patients than in the HD group (2.88±1.2 μmol/L/h versus 3.79±1.9 μmol/L/h, p<0.001). There was no significant relationship between the two groups with regard to the plasma LysoGb3 levels (2.2±1.22 ng/ml versus 1.7±0.66 ng/ml, p: 0.4). In the analysis of GLA mutations, a D313Y mutation [C(937G>T) in exon p] was found in one patient from the FSGS group. CONCLUSIONS: We found that αGAL activity in patients with FSGS is lower than that in patients undergoing HD. The low enzyme activity in patients with FSGS may be explained by considering the similar pathogenesis of FSGS and FD, which may also lead to sphingolipid deposition and podocyte injury.

Pentraxin-2 is associated with renal fibrosis in patients undergoing renal biopsy

OBJECTIVES: Progressive renal disease is characterized by histological changes in the kidney and fibrosis is a common outcome. Renal biopsy is the only diagnostic tool to evaluate these histopathological changes. Pentraxin-2 (PTX-2) is an anti-inflammatory constitutive plasma protein associated with the innate immune system. Recently, as a biomarker, the circulating level of PTX-2 is shown to be decreased in chronic fibrotic diseases. In this study, we aimed to investigate the relationship between renal fibrosis severity and serum PTX-2 levels in patients undergoing renal biopsy. METHODS: This cross-sectional study included 45 patients and 16 healthy individuals (HIs). The severity of renal fibrosis was evaluated according to the Banff and Sethi scoring systems by the same pathologist. PTX-2 was measured by an enzyme-linked immunosorbent assay and compared with the demographical, clinical, biochemical, and histopathological data of the patients and HIs. RESULTS: PTX-2 levels were lower in the biopsy group than in the HI group (p=0.12). Patients with moderate renal fibrosis had significantly lower serum PTX-2 levels than those in patients with minimal and mild fibrosis (p=0.017 and p=0.010, respectively). PTX-2 concentrations were correlated with serum albumin (r=0.30, p=0.016), and were negatively correlated with serum creatinine levels (rho=-0.42, p=0.01) and body mass index (r=-0.32, p=0.011). CONCLUSIONS: The results indicated that PTX-2 levels are significantly lower in patients with renal fibrosis than HIs, and declining further in patients with severe fibrosis.

The relationship between serum albumin levels and 24-h ambulatory blood pressure monitoring recordings in non-diabetic essential hypertensive patients

OBJECTIVES: The goal of this study was to evaluate the relationship between serum albumin levels and 24-hour ambulatory blood pressure monitoring (24-h ABPM) recordings in non-diabetic essential hypertensive patients. METHODS: A total of 354 patients (mean [SD] age: 55.5 [14.3] years, 50% females) with essential hypertension and 24-h ABPM recordings were included. Patient 24-h nighttime and daytime ABPM values, systolic and diastolic dipping status and average nocturnal dipping were recorded. The correlations between serum albumin levels and nocturnal systolic and diastolic dipping were evaluated, and correlates of average nocturnal systolic dipping were determined via a linear regression model. RESULTS: Overall, 73.2% of patients were determined to be non-dippers. The mean (SD) levels of serum albumin (4.2 [0.3] g/dL vs. 4.4 [0.4] g/dL, p<0.001) and the average nocturnal systolic (15.2 [4.8] mmHg vs. 0.3 [6.6] mmHg, p<0.001) and diastolic dipping (4.2 [8.6] mmHg vs. 18.9 [7.0] mmHg, p<0.001) were significantly lower in non-dippers than in dippers. A significant positive correlation was noted between serum albumin levels and both systolic (r=0.297, p<0.001) and diastolic dipping (r=0.265, p<0.001). The linear regression analysis revealed that for each one-unit increase in serum albumin, the average nocturnal dip in systolic BP increased by 0.17 mmHg (p=0.033). CONCLUSION: Our findings indicate an association between serum albumin levels and the deterioration of circadian BP rhythm among essential hypertensive patients along with the identification of a non-dipper pattern in more than two-thirds of patients. Our findings emphasize the importance of serum albumin levels, rather than urinary albumin excretion, as an independent predictor of nocturnal systolic dipping, at least in non-diabetic essential hypertensive patients with moderate proteinuria.

Familial Mediterranean Fever is associated with abnormal ventricular repolarization indices / La fiebre mediterránea familiar se asocia a anomalías en la repolarizacıón ventricular

Background: Cardiac arrhythmias can be a part of cardiovascular involvement in some rheumatic diseases, but data about familial Mediterranean fever (FMF) are conflicting. Aim: To search for abnormalities in ventricular repolarization indices in FMF patients. Patients and Methods: Seventy seven FMF patients and 30 age/gender comparable healthy controls were included. All patients were attack free and subjects with disease or drugs that are known to alter cardiac electrophysiology were excluded. Electrocardiographic data were obtained and analyzed. Results: Twelve FMF patients had amyloidosis. QT and QTc intervals were within the normal ranges and similar between FMF patients and healthy controls. QT dispersion, peak to end interval of T wave (Tpe), Tpe/QT and Tpe/QTc ratios were significantly higher in FMF patients than in healthy controls. Patients with amyloidosis had significantly higher QT dispersion, Tpe, Tpe/QT and Tpe/QTc than their counterparts without FMF. Levels of proteinuria were moderately correlated with QT dispersion, Tpe, Tpe/QT and Tpe/QTc. Conclusions: FMF patients may have an increased risk for arrhythmias.

Antecedentes: Las arritmias cardíacas pueden ser parte del compromiso cardíaco en enfermedades reumáticas, sin embargo, no se sabe con certeza si esto ocurre en la fiebre mediterránea familiar (FMF). Objetivo: Buscar anomalías en la repolarización ventricular en pacientes con FMF. Pacientes y Métodos: Sesenta y siete pacientes como FMF y 30 controles sanos pareados por edad y género fueron estudiados. Todos los pacientes estaban en período intercrítico y no usaban medicamentos o tenían enfermedades concomitantes que pudieran causar anomalías electrocardiográficas. Se analizaron los electrocardiogramas de estos participantes. Resultados: Veinte pacientes con FMF tenían amiloidosis. Los intervalos QT y QTc eran normales y similares entre pacientes y controles. La dispersión del intervalo QT, el intervalo desde el peak al final de la onda T (Tpe), las razones Tpe/QT y Tpe/QTc fueron significativamente más altos en los pacientes que en los controles. Los pacientes con amiloidosis tenían una dispersión de QT, Tpe, Tpe/QT y Tpe/QTc mayores que sus pares sin la condición. Los niveles de proteinuria se correlacionaron moderadamente con los parámetros antes mencionados. Conclusiones: Los pacientes con FMF tienen mayor riesgo de arritmias.

Clinical outcomes and mortality in elderly peritoneal dialysis patients

OBJECTIVES: To evaluate the clinical outcomes and identify the predictors of mortality in elderly patients undergoing peritoneal dialysis. METHODS: We conducted a retrospective study including all incident peritoneal dialysis cases in patients ≥65 years of age treated from 2001 to 2014. Demographic and clinical data on the initiation of peritoneal dialysis and the clinical events during the study period were collected. Infectious complications were recorded. Overall and technique survival rates were analyzed. RESULTS: Fifty-eight patients who began peritoneal dialysis during the study period were considered for analysis, and 50 of these patients were included in the final analysis. Peritoneal dialysis exchanges were performed by another person for 65% of the patients, whereas 79.9% of patients preferred to perform the peritoneal dialysis themselves. Peritonitis and catheter exit site/tunnel infection incidences were 20.4±16.3 and 24.6±17.4 patient-months, respectively. During the follow-up period, 40 patients were withdrawn from peritoneal dialysis. Causes of death included peritonitis and/or sepsis (50%) and cardiovascular events (30%). The mean patient survival time was 38.9±4.3 months, and the survival rates were 78.8%, 66.8%, 50.9% and 19.5% at 1, 2, 3 and 4 years after peritoneal dialysis initiation, respectively. Advanced age, the presence of additional diseases, increased episodes of peritonitis, the use of continuous ambulatory peritoneal dialysis, and low albumin levels and daily urine volumes (<100 ml) at the initiation of peritoneal dialysis were predictors of mortality. The mean technique survival duration was 61.7±5.2 months. The technique survival rates were 97.9%, 90.6%, 81.5% and 71% at 1, 2, 3 and 4 years, respectively. None of the factors analyzed were predictors of technique survival. CONCLUSIONS: Mortality was higher in elderly patients. Factors affecting mortality in elderly patients included advanced age, ...

The effects of angiotensin-converting enzyme inhibitors on peritoneal protein loss and solute transport in peritoneal dialysis patients

OBJECTIVE: The objective of this study was to examine the effects of angiotensin-converting enzyme inhibitors on peritoneal membrane transport, peritoneal protein loss, and proteinuria in peritoneal dialysis patients. METHODS: Fifty-four peritoneal dialysis patients were included in the study. The patients were divided into two groups. Group 1 (n = 34) was treated with angiotensin-converting enzyme inhibitors. Group 2 (n = 20) did not receive any antihypertensive drugs during the entire follow-up. Eleven patients were excluded from the study thereafter. Thus, a total of 30 patients in Group 1 and 13 patients in Group 2 completed the study. We observed the patients for six months. Group 1 patients received maximal doses of angiotensin-converting enzyme inhibitors for six months. Parameters at the beginning of study and at the end of six months were evaluated. RESULTS: At the end of six months, total peritoneal protein loss in 24-hour dialysate effluent was significantly decreased in Group 1, whereas it was increased in Group 2. Compared to the baseline level, peritoneal albumin loss in 24-hour dialysate effluent and 4-hour D/P creatinine were significantly increased in Group 2 but were not significantly changed in Group 1. A covariance analysis between the groups revealed a significant difference only in the decreased amount of total protein loss in 24-hour dialysate. Proteinuria was decreased significantly in Group 1. CONCLUSION: This study suggests that angiotensin-converting enzyme inhibitors reduce peritoneal protein loss and small-solute transport and effectively protect peritoneal membrane transport in peritoneal dialysis patients.