Urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL) Predicts Renal Function Decline in Patients With Glomerular Diseases.

OBJECTIVE: Available biomarkers for monitoring primary glomerulonephritides (GNs), often lack the ability to assess longitudinal changes and have great variability with poor sensitivity. Accruing evidence has demonstrated that Neutrophil Gelatinase-Associated Lipocalin (NGAL), holds promising capacities in predicting renal function worsening in various renal diseases. We aimed at analyzing urinary NGAL (uNGAL) levels in a cohort of individuals with biopsy-proven GNs in order to evaluate its ability to reflect the entity of renal damage and to predict disease evolution overtime. METHODS: We enrolled 61 consecutive GNs patients still naïve to pathogenic therapy. uNGAL levels were measured at baseline and patients prospectively followed until the manifestation of a combined outcome of doubling of baseline serum creatinine and/or end-stage kidney disease requiring permanent dialysis support. RESULTS: Median uNGAL levels were 107[35-312] ng/mL. At univariate and multivariate analyses an inverse correlation was found between eGFR and uNGAL levels (p = 0.001). Progressor subjects showed exceedingly increased baseline uNGAL values as compared with non-progressors (p < 0.001). Twenty-one patients (34%) reached the composite renal endpoint. Subjects with uNGAL values above the optimal, ROC-derived, cut-off of 107 ng/mL experienced a more rapid progression to the renal endpoint (p < 0.001; HR: 5.47; 95% CI 2.31-12.95) with a mean follow-up time to progression of 73.4 vs 83.5 months. CONCLUSION: In patients affected by primary glomerulonephritides, uNGAL may represent a real-time indicator of renal damage and an independent predictor of renal disease progression. Further studies on larger populations are warranted to confirm these findings.

Renal resistive index in chronic kidney disease patients: Possible determinants and risk profile.

BACKGROUND: High ultrasound renal resistive index (RI) predicts poor cardiorenal outcomes in chronic kidney disease (CKD) and has recently emerged as a marker of nephroprotective drugs response. Thus, having a risk profile of CKD patients with abnormal RI may be relevant for the clinicians. METHODS: Consecutive patients referred to our non-dialysis CKD clinic from 01/01/2016 to 01/12/2016, were evaluated by clinical and ultrasound analysis. Inclusion criteria were age >18 years and presence of CKD defined as estimated glomerular filtration rate (eGFR)<60 mL/min/1.73m2 and/or proteinuria>0.150g/24h. Renal artery stenosis, solitary kidney, acute kidney injury were the main exclusion criteria. RI value was the mean of three measures in segmental arteries in each kidney. Univariate analysis was performed to evaluate associations between continuous RI and clinical variables. Multivariate linear regression analysis, based on stepwise method with an elimination criterion of p<0.10, was used to assess the independent correlates of RI as continuous variable. RESULTS: We studied 73 patients (69.9% men). Mean RI was 0.67±0.09. Frequencies of diabetes and cardiovascular disease (CVD) were 19.2% and 20.6% and median eGFR 54.1 [30.0-84.6] mL/min/1.73m2. From low (<0.65) to intermediate (0.65-0.70) to high (>0.70) RI categories, eGFR and haemoglobin levels were decreased while diabetes, cardiovascular disease (CVD), phosphate and smokers were higher. At univariate analysis, RI was significantly associated with age, presence of diabetes, CVD, serum phosphorus, eGFR, Urea and haemoglobin. Multi-adjusted stepwise regression analysis showed that lower eGFR levels (p<0.001), diabetes (p = 0.042), CVD (p = 0.009), smoking habit (p = 0.021) and higher serum phosphorus levels (p = 0.001) were associated with higher continuous RI. Serum phosphorus showed Area Under the Curves (AUC) values of 0.714 and 0.664 for discriminating RI cut-offs of 0.70 and 0.65. CONCLUSIONS: This analysis suggests that RI is higher in CKD patients with CVD, diabetes, smoking habit and higher serum phosphorus, regardless of eGFR. Further studies are needed to verify whether higher RI indicates more complex pathway of intrarenal damage, besides and beyond kidney function.

Utility of Blood Flow/Resistance Index Ratio (Qx) as a Marker of Stenosis and Future Thrombotic Events in Native Arteriovenous Fistulas.

Objective: The resistance index (RI) and the blood flow volume (Qa) are the most used Doppler ultrasound (DUS) parameters to identify the presence of stenosis in arteriovenous fistula (AVF). However, the reliability of these indexes is now matter of concern, particularly in predicting subsequent thrombosis. In this study, we aimed at testing the diagnostic capacity of the Qa/RI ratio (Qx) for the early identification of AVF stenosis and for thrombosis risk stratification. Methods: From a multicentre source population of 336 HD patients, we identified 119 patients presenting at least one "alarm sign" for clinical suspicious of stenosis. Patients were therefore categorized by DUS as stenotic (n = 60) or not-stenotic (n = 59) and prospectively followed. Qa, RI, and QX, together with various clinical and laboratory parameters, were recorded. Results: Qa and Qx were significantly higher while RI was significantly lower in non-stenotic vs. stenotic patients (p < 0.001 for each comparison). At ROC analyses, Qx had the best discriminatory power in identifying the presence of stenosis as compared to Qa and RI (AUCs 0.976 vs. 0.953 and 0.804; p = 0.037 and p < 0.0001, respectively). During follow-up, we registered 30 thrombotic events with an incidence rate of 12.65 (95% CI 8.54-18.06) per 100 patients/year. In Cox-regression proportional hazard models, Qx showed a better capacity to predict thrombosis occurrence as compared to Qa (difference between c-indexes: 0.012; 95% CI 0.004-0.01). Conclusions: In chronic haemodialysis patients, Qx might represent a more reliable and valid indicator for the early identification of stenotic AVFs and for predicting the risk of following thrombosis.

Erythropoiesis and chronic kidney disease-related anemia: From physiology to new therapeutic advancements.

Erythropoiesis is triggered by hypoxia and is strictly regulated by hormones, growth factors, cytokines, and vitamins to ensure an adequate oxygen delivery to all body cells. Abnormalities in one or more of these factors may induce different kinds of anemia requiring different treatments. A key player in red blood cell production is erythropoietin. It is a glycoprotein hormone, mainly produced by the kidneys, that promotes erythroid progenitor cell survival and differentiation in the bone marrow and regulates iron metabolism. A deficit in erythropoietin synthesis is the main cause of the normochromic normocytic anemia frequently observed in patients with progressive chronic kidney disease. The present review summarizes the most recent findings about each step of the erythropoietic process, going from the renal oxygen sensing system to the cascade of events induced by erythropoietin through its own receptor in the bone marrow. The paper also describes the new class of drugs designed to stabilize the hypoxia-inducible factor by inhibiting prolyl hydroxylase, with a discussion about their metabolism, disposition, efficacy, and safety. According to many trials, these drugs seem able to simulate tissue hypoxia and then stimulate erythropoiesis in patients affected by renal impairment. In conclusion, the in-depth investigation of all events involved in erythropoiesis is crucial to understand anemia pathophysiology and to identify new therapeutic strategies, in an attempt to overcome the potential side effects of the commonly used erythropoiesis-stimulating agents.

Evolution of glomerular filtration rates and neutrophil gelatinase-associated lipocalin during treatment with direct acting antivirals.

Background/Aims: Correct renal function evaluation is based on estimated glomerular filtration rates (eGFR) and complementary renal damage biomarkers, such as neutrophil gelatinase associated lipocalin (NGAL). The aim of this study was to evaluate eGFR and NGAL modifications and renal impairment during treatment with a direct acting antiviral (DAA) for chronic hepatitis C virus (HCV) infection. METHODS: A retrospective cohort study evaluated eGFR modification during treatment with DAA. Subgroup analysis on serum NGAL was conducted in those receiving sofosbuvir/ledipasvir, with complete follow-up until week 12 after the end of treatment (FU-12). RESULTS: In the 102 enrolled patients, eGFR reduction was observed (from 86.22 mL/min at baseline to 84.43 mL/min at FU-12, P=0.049). Mean NGAL increased in 18 patients (from 121.89 ng/mL at baseline to 204.13 ng/mL at FU-12, P=0.014). At FU-12, 38.8% (7/18) of patients had a plasmatic NGAL value higher than the normal range (36-203 ng/mL) compared with 11.1% (2/18) at baseline (χ 2 =3,704; P=0.054). In contrast, eGFR did not change significantly over the follow-up in this subgroup. Conclusions: In conclusion, compared to a negligible eGFR decline observed in the entire cohort analyzed, a significant NGAL increase was observed after HCV treatment with DAA in a small subgroup. This could reflect tubular damage during DAA treatment rather than glomerular injury.

[A cause of acute renal dysfunction: a giant bladder diverticulum].

We describe the case of a previously 77-year-old man who accessed in our Nephrology Unit for acute kidney injury (AKI) on chronic kidney disease (CKD), gastric discomfort and vague urinary symptoms with apparently preserved diuresis and suspected "ascites". Physical examination confirmed the presence of abdominal effusion, even though ultrasound abdominal examination revealed the presence of a giant diverticular urinary bladder with bilateral hydronephrosis. We discuss the diagnostic and therapeutic approach of these rare complications by briefly reviewing the technical aspects and the possible consequences.

Tumour markers and kidney function: a systematic review.

Tumour markers represent useful tools in diagnosis and clinical management of patients with cancer, because they are easy to use, minimally invasive, and easily measured in either blood or urine. Unfortunately, such an ideal marker, as yet, does not exist. Different pathological states may increase the level of a tumour marker in the absence of any neoplasia. Alternatively, low levels of tumour markers could be also found in the presence of neoplasias. We aimed at reviewing studies currently available in the literature examining the association between tumour markers and different renal impairment conditions. Each tumour marker was found to be differently influenced by these criteria; additionally we revealed in many cases a lack of available published data.

The risk of a persistent glucose metabolism impairment after gestational diabetes mellitus is increased in patients with polycystic ovary syndrome.

OBJECTIVE: To test the hypothesis that the risk of persistent glucose impairment after gestational diabetes mellitus (GDM) is increased in patients with polycystic ovary syndrome (PCOS). RESEARCH DESIGN AND METHODS: The prospective case-control study included 42 pregnant patients with PCOS and GDM and 84 pregnant control patients with GDM but without clinical and biochemical hyperandrogenism, polycystic ovaries, and oligo-anovulation. The case and control subjects were matched one to two for age and BMI. The glycemic profiles were studied in all subjects 6 weeks, 12 weeks, and 18 months after delivery. The incidence and the relative risk (RR) were calculated for overall persistence of an abnormal glycemic pattern and for each specific alteration, i.e., impaired glucose tolerance (IGT), impaired fasting glucose (IFG), and diabetes mellitus (DM). RESULTS: At 18 months after delivery, the incidences of IFG, IGT, and IFG-IGT were significantly (P < 0.05) higher in the cases than in the controls. At the 18-month follow-up, the RR for the composite outcome of glucose metabolism impairment in PCOS women was 3.45 (95% CI 1.82-6.58). CONCLUSIONS: Patients with PCOS are at increased risk for a persistent impaired glucose metabolism after GDM.