Urinary chemokine C-X-C motif ligand 16 and endostatin as predictors of tubulointerstitial fibrosis in patients with advanced diabetic kidney disease.

BACKGROUND: Interstitial fibrosis and tubular atrophy (IFTA) is a well-recognized risk factor for poor renal outcome in patients with diabetic kidney disease (DKD). However, a noninvasive biomarker for IFTA is currently lacking. The purpose of this study was to identify urinary markers of IFTA and to determine their clinical relevance as predictors of renal prognosis. METHODS: Seventy patients with biopsy-proven isolated DKD were enrolled in this study. We measured multiple urinary inflammatory cytokines and chemokines by multiplex enzyme-linked immunosorbent assay in these patients and evaluated their association with various pathologic features and renal outcomes. RESULTS: Patients enrolled in this study exhibited advanced DKD at the time of renal biopsy, characterized by moderate to severe renal dysfunction [mean estimated glomerular filtration rate (eGFR) 36.1 mL/min/1.73 m2] and heavy proteinuria (mean urinary protein:creatinine ratio 7.8 g/g creatinine). Clinicopathologic analysis revealed that higher IFTA scores were associated with worse baseline eGFR (P < 0.001) and poor renal outcome (P = 0.002), whereas glomerular injury scores were not. Among measured urinary inflammatory markers, C-X-C motif ligand 16 (CXCL16) and endostatin showed strong correlations with IFTA scores (P = 0.001 and P < 0.001, respectively), and patients with higher levels of urinary CXCL16 and/or endostatin experienced significantly rapid renal progression compared with other patients (P < 0.001). Finally, increased urinary CXCL16 and endostatin were independent risk factors for poor renal outcome after multivariate adjustments (95% confidence interval 1.070-3.455, P = 0.029). CONCLUSIONS: Urinary CXCL16 and endostatin could reflect the degree of IFTA and serve as biomarkers of renal outcome in patients with advanced DKD.

Changes in mortality hazard of the Korean long-term dialysis population: The dependencies of time and modality switch.

BACKGROUND: Many studies have compared patient survival outcome between hemodialysis (HD) and peritoneal dialysis (PD); however, time-varying risks of dialysis modality have been rarely investigated. This study aimed to investigate dialysis modality switch and its association with the survival outcome in the Korean population. METHODS: Data from the Korean Society of Nephrology were used. A total of 21,840 incident dialysis patients who started dialysis in or after 2000 were analyzed. For the survival analysis, both proportional and non-proportional hazard assumptions were applied. For the modality switch, time-varying covariate Cox regression was applied. RESULTS: During the median follow-up of 8 years, PD group showed increased adjusted hazard ratio (HR) of 1.248 (95% CI 1.071-1.454, p = 0.004) for mortality. Interaction of PD status with female sex was significant with an HR of 1.080 (95% CI 1.000-1.165, p = 0.050). Dialysis modality switch was associated with increased HR of 1.094 (95% CI 1.015-1.180, p = 0.019), albeit switch from PD to HD did not show significant HR until 6 years. Interestingly, time-varying risk analysis showed a decreased HR of PD after 10 years in the non-switcher group, which was consistent in patients with high traditional risk factors (with diabetes, elderly). CONCLUSIONS: PD was associated with increased HR of mortality in the first 8 years, then it was associated with decreased HR of mortality after 10 years. Dialysis modality switch was associated with increased mortality risk, but switch from PD to HD within 6 years did not show significant hazard of mortality.

The Role of Inflammasome-Dependent and Inflammasome-Independent NLRP3 in the Kidney.

Cytoplasmic nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) forms an inflammasome with apoptosis-associated speck-like protein containing a CARD (ASC) and pro-caspase-1, which is followed by the cleavage of pro-caspase-1 to active caspase-1 and ultimately the activation of IL-1ß and IL-18 and induction of pyroptosis in immune cells. NLRP3 activation in kidney diseases aggravates inflammation and subsequent fibrosis, and this effect is abrogated by genetic or pharmacologic deletion of NLRP3. Inflammasome-dependent NLRP3 mediates the progression of kidney diseases by escalating the inflammatory response in immune cells and the cross-talk between immune cells and renal nonimmune cells. However, recent studies have suggested that NLRP3 has several inflammasome-independent functions in the kidney. Inflammasome-independent NLRP3 regulates apoptosis in tubular epithelial cells by interacting with mitochondria and mediating mitochondrial reactive oxygen species production and mitophagy. This review will summarize the mechanisms by which NLRP3 functions in the kidney in both inflammasome-dependent and inflammasome-independent ways and the role of NLRP3 and NLRP3 inhibitors in kidney diseases.

Clinicopathological features of diabetic and nondiabetic renal diseases in type 2 diabetic patients with nephrotic-range proteinuria.

Heavy proteinuria with or without features of nephrotic syndrome is associated with many primary and systemic diseases. For diabetic patients, distinguishing nondiabetic renal disease (NDRD) from diabetic nephropathy (DN) is important in choosing treatment modalities and determining renal prognosis. However, clinical relevance of heavy proteinuria is inconsistent with clinical DN assessments. This study investigated the clinicopathological features and renal outcomes of DN and NDRD in type 2 diabetic patients with nephrotic-range proteinuria.We enrolled 220 cases of type 2 diabetic patients who underwent renal biopsy. They were grouped according to the presence of nephritic-range proteinuria and pathological features. Baseline characteristics, laboratory findings, types of pathological diagnosis, and renal outcomes were analyzed in patients with heavy proteinuria.Upon kidney biopsy, 129 patients (58.6%) showed nephritic-range proteinuria. Patients with heavy proteinuria (an average urine protein-to-creatinine ratio of 10,008 ±â€Š7307 mg/gCr) showed lower serum albumin levels and higher total cholesterol levels, but did not show any difference in age, duration of diabetes, renal function, or the presence of retinopathy compared with those with mild-to-moderate proteinuria (an average urine protein-to-creatinine ratio of 1581 ±â€Š979 mg/gCr). Renal biopsy revealed that the prevalence of NDRD was 37.2% in patients with heavy proteinuria, which was significantly lower than that in patients with mild-to-moderate proteinuria (63.7%). The most common pathological types of NDRD were membranous nephropathy (41.7%), IgA nephropathy (14.6%), and minimal change disease (10.4%). NDRD patients showed lower prevalence of diabetic retinopathy and better kidney function irrespective of proteinuria. Immunosuppressive treatment was administered more frequently in patients with heavy proteinuria (56.3%) compared with patients with mild-to-moderate proteinuria (20%) because of the pathological differences according to the amount of proteinuria. Renal outcomes were significantly worse in patients with DN than in patients with NDRD.DN patients with heavy proteinuria exhibited different prevalence of NDRD and worse prognosis. Renal biopsy in type 2 diabetic patients should be more extensively considered to accurately diagnose NDRD, guide further management, and predict renal outcomes, especially in patients with nephrotic-range proteinuria.

Bilateral Spontaneous Perirenal Hemorrhage due to Initial Presentation of Polyarteritis Nodosa.

Spontaneous perirenal hemorrhage (SPH) is uncommon but can be a life-threatening condition which is associated with flank or abdominal pain and hypovolemia. The etiologies of SPH include tumor, vascular disease, and infection. Among the vascular diseases, polyarteritis nodosa (PAN) is common cause of the SPH. However, patients with PAN usually complain of nonspecific symptoms and the incidence of PAN is relatively rare. So, diagnosis is difficult even though tissue biopsy and angiography help to confirm the PAN. Particularly bilateral perirenal hemorrhage is very rare complication in patients with PAN. We reported a case of bilateral perirenal hemorrhage in the patients with PAN who have continued to take exogenous sex hormone.