Development Of Chronic Kidney Disease Stage Research Articles

#594 Long-term risk of incident/progressive chronic kidney disease, or end-stage kidney disease post-acute kidney injury: systematic review, meta-analysis

Abstract Background and Aims Little is known about which patients to follow-up after an episode of acute kidney injury (AKI) for future risks. The aim of this review is to assess the association between AKI and the incidence or progression of chronic kidney disease (CKD) or end-stage kidney disease (ESKD), stratified by subcategories of AKI-stages, -durations, and clinical settings. Method A systematic search of the literature in PubMed and Embase was performed by two reviewers to identify studies that examined CKD incidence (development of CKD stage ≥3), CKD progression (worsening of kidney function in patients with CKD stage ≥3), or ESKD, in patients with AKI versus patients without AKI. The risk of bias was assessed using the Newcastle-Ottawa Scale. Relative effect estimates (odds and hazard ratios) were pooled using a random effects model. Results In total, 48 retrospective and 13 prospective studies, encompassing 140.985 patients with AKI, were included in this review. All the studies were of moderate or high quality. The pooled effect ratio was 3.36 (95% confidence interval (CI) 2.68-4.03) for CKD incidence (n = 31 studies). This remained 3.40 (95% CI 1.79-5.00) in a sub analysis including patients with a recovered kidney function post-AKI, and 1.49 (95% CI 1.44-1.55) in a sub analysis including patients with an AKI lasting less than 3 days (Fig. 1). Overall, the effect ratio for CKD progression (n = 11 studies) was 1.70 (95% CI 1.38-2.01) and 3.81 (95% CI 2.58-5.04) for ESKD (n = 24 studies). The increased risk of these two outcomes were not seen in the sub analyses only including patients with AKI lasting less than 3 days. Overall, there is an observable higher risk for CKD incidence, CKD progression, and ESKD with increased AKI staging, although not always statistically significant. Minimal variations were observed across clinical settings. Conclusion In our review, including over 60 studies, we found that AKI was associated with an increased risk of CKD incidence, CKD progression, and ESKD. Patients with higher AKI-stages had even larger risks. Notably, even brief episodes of AKI (lasting less than 3 days) were associated with a higher risk of CKD incidence compared to patients without AKI. In contrary, the risk for ESKD is not enlarged in a sub analysis including patients with recovered kidney function compared to patients without AKI. These result warrant close monitoring of the kidney function post-AKI, specifically in patients with AKI lasting 3 days or longer. Future research should focus more on the risk of CKD progression in order to tailor follow-up care in these more vulnerable patients.

Impact of age on functional decline following radical nephrectomy: Analysis of the International Marker Consortium for Renal Cancer (INMARC).

395 Background: Radical nephrectomy (RN) is a mainstay of management of localized renal cancer larger than 4 cm in size. RN is associated with renal functional decline, however impact of age on functional decline is unclear. We investigated impact of age on post RN function, focusing on decline to moderate and severe chronic kidney disease (CKD). Methods: This was a retrospective analysis of the International Marker Consortium for Renal Cancer (INMARC) registry of patients who underwent RN. Primary outcome was development of de novo CKD stage IIIB [estimated glomerular filtration rate (eGFR)<45 mL/min/1.73m2). Secondary outcomes included de novo CKD stage III (eGFR<60) and CKD Stage IV (eGFR>30). Patients clinical characteristics were stratified by age groups (<50, 50-70 and >70 years old). Multivariable logistic regression analysis (MVA) was utilized to identify risk factors with renal functional decline to different CKD stages. Kaplan-Meier analysis (KMA) was utilized to evaluate functional outcomes with respect to the different age groups. Results: Overall, 2,436 patients were analyzed (≤50 years, n=513; 50-70 years, n=1,344; >70, n=579; median follow up 31.9 months). On MVA, increasing age was independently associated with increased risk of development of CKD Stage IIIb [compared to ≤50 years (referent), 50-70 years, OR 3.35, p<0.001 and >70 years OR 7.7, p<0.001]. In addition, increasing BMI (OR 1.029, p=0.002), coronary artery disease (OR 1.70, p=0.01), diabetes mellitus (OR 1.37, p=0.029) and African American race (OR 1.6, p=0.01) were independent risk factors for CKD stage IIIb. Increasing age was also independently associated with an increased risk of development of CKD Stage III [compared to ≤50 years (referent), 50-70 years, OR 3.4 p<0.001 and >70 years OR 9.4, p<0.001]. Increasing BMI (OR 1.032, p=0.002) and coronary artery disease (OR 1.87, p=0.015) were also risk factors for CKD stage III. Age >70 years was independently associated with increased risk of development of CKD Stage IV [OR 1.96, p=0.027]. In addition, male (OR 1.49, p= 0.036), increasing BMI (OR 1.03, p=0.003), diabetes mellitus (OR 2.69, p <0.001), and African American race (OR 2.02, p=0.002) were risk factors for CKD stage IV. Kaplan-Meier Analyses demonstrated age associated declines in 5 year freedom from CKD Stage III (≤50 years 73.9%, 50-70 years 53.7%, and >70 years 37.06%, p<0.001), CKD Stage IIIb (age ≤50 years 92.7%, 50-70 years 71.8%, and >70 years 55.5%, p<0.001) and CKD Stage IV (age ≤50 years 93.7%, 50-70 years 89.8%, and >70 years 81.2%, p< 0.001). Conclusions: Increasing age is an independent risk factor for progressive and clinically significant renal functional decline after radical nephrectomy. Prioritization for nephron sparing management should be considered whenever safe and feasible in elderly patients to reduce potential risk of sequelae of functional decline.

Outcome of kidney function after ischaemic and zero-ischaemic laparoscopic and open nephron-sparing surgery for renal cell cancer

BackgroundNephron-sparing surgery (NSS) remains gold standard for the treatment of localised renal cell cancer (RCC), even in case of a normal contralateral kidney. Compared to radical nephrectomy, kidney failure and cardiovascular events are less frequent with NSS. However, the effects of different surgical approaches and of zero ischaemia on the postoperative reduction in renal function remain controversial.We aimed to investigate the relative short- and long-term changes in estimated glomerular filtration rate (eGFR) after ischaemic or zero-ischaemic open (ONSS) and laparoscopic NSS (LNSS) for RCC, and to analyse prognostic factors for postoperative acute kidney injury (AKI) and chronic kidney disease (CKD) stage ≥3.MethodsData of 444 patients (211 LNSS, 233 ONSS), including 57 zero-ischaemic cases, were retrospectively analysed. Multiple regression models were used to predict relative changes in renal function. Natural cubic splines were used to demonstrate the association between ischaemia time (IT) and relative changes in renal function.ResultsIT was identified as significant risk factor for short-term relative changes in eGFR (ß = − 0.27) and development of AKI (OR, 1.02), but no effect was found on long-term relative changes in eGFR. Natural cubic splines revealed that IT had a greater effect on patients with baseline eGFR categories ≥G3 concerning short-term decrease in renal function and development of AKI. Unlike LNSS, ONSS was significantly associated with short-term decrease in renal function (ß = − 13.48) and development of AKI (OR, 3.87). Tumour diameter was associated with long-term decrease in renal function (ß = − 1.76), whereas baseline eGFR was a prognostic factor for both short- (ß = − 0.20) and long-term (ß = − 0.29) relative changes in eGFR and the development of CKD stage ≥3 (OR, 0.89).ConclusionsIT is a significant risk factor for AKI. The short-term effect of IT is not always linear, and the impact also depends on baseline eGFR. Unlike LNSS, ONSS is associated with the development of AKI. Our findings are helpful for surgical planning, and suggest either the application of a clampless NSS technique or at least the shortest possible IT to reduce the risk of short-time impairment of the renal function, which might prevent AKI, particularly regarding patients with baseline eGFR category ≥G3.

Risk of chronic kidney disease in patients with gout and the impact of urate lowering therapy: a population-based cohort study

BackgroundAn association between gout and renal disease is well-recognised but few studies have examined whether gout is a risk factor for subsequent chronic kidney disease (CKD). Additionally, the impact of urate-lowering therapy (ULT) on development of CKD in gout is unclear. The objective of this study was to quantify the risk of CKD stage ≥ 3 in people with gout and the impact of ULT.MethodsThis was a retrospective cohort study using data from the Clinical Practice Research Datalink (CPRD). Patients with incident gout were identified from general practice medical records between 1998 and 2016 and randomly matched 1:1 to patients without a diagnosis of gout based on age, gender, available follow-up time and practice. Primary outcome was development of CKD stage ≥ 3 based on estimated glomerular filtration rate (eGFR) or recorded diagnosis. Absolute rates (ARs) and adjusted hazard ratios (HRs) were calculated using Cox regression models. Risk of developing CKD was assessed among those prescribed ULT within 1 and 3 years of gout diagnosis.ResultsPatients with incident gout (n = 41,446) were matched to patients without gout. Development of CKD stage ≥ 3 was greater in the exposed group than in the unexposed group (AR 28.6 versus 15.8 per 10,000 person-years). Gout was associated with an increased risk of incident CKD (adjusted HR 1.78 95% CI 1.70 to 1.85). Those exposed to ULT had a greater risk of incident CKD, but following adjustment this was attenuated to non-significance in all analyses (except on 3-year analysis of women (adjusted HR 1.31 95% CI 1.09 to 1.59)).ConclusionsThis study has demonstrated gout to be a risk factor for incident CKD stage ≥ 3. Further research examining the mechanisms by which gout may increase risk of CKD and whether optimal use of ULT can reduce the risk or progression of CKD in gout is suggested.

Baseline total kidney volume and the rate of kidney growth are associated with chronic kidney disease progression in Autosomal Dominant Polycystic Kidney Disease

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive enlargement of kidney cysts leading to chronic kidney disease (CKD) and end-stage renal disease (ESRD). Identification of an early biomarker that can predict progression of CKD is urgently needed. In an earlier Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP) study (a prospective, multicenter, observational analysis of 241 patients with ADPKD initiated in 2000), baseline height-adjusted total kidney volume (htTKV) was shown to be associated with development of CKD stage 3 after eight years of follow-up. Here we conducted an extended study and found that in a multivariable logistic regression model, baseline htTKV was shown to be a strong, independent predictor for the development of CKD after a median follow-up of 13 years. The odds ratio of reaching each CKD stage per 100 mL/m increment in htTKV was 1.38 (95% confidence interval 1.19-1.60) for stage 3, 1.42 (1.23-1.64) for stage 4, and 1.35 (1.18-1.55) for stage 5 or ESRD. Baseline htTKV was also associated with relative decreases in the glomerular filtration rate of 30%, and 57% or more. Moreover, the rate of change in htTKV was negatively correlated with the slope of the glomerular filtration rate. While ADPKD genotype was also associated with CKD outcomes, it was not an independent prognostic factor after adjusting for htTKV. Thus, baseline total kidney volume and the rate of kidney growth are strongly associated with the development of advanced stages of CKD. These findings support the use of total kidney volume as a prognostic and potentially monitoring biomarker in ADPKD.

Low serum bilirubin level predicts the development of chronic kidney disease in patients with type 2 diabetes mellitus.

Background/AimsWe evaluated whether serum bilirubin levels can predict the development of chronic kidney disease (CKD) in patients with type 2 diabetes mellitus (T2DM).MethodsThis was a retrospective observational longitudinal study of patients presenting at the Pusan National University Hospital. A total of 349 patients with T2DM and preserved kidney function (estimated glomerular filtration rate ≥ 60 mL/min/1.73 m2) were enrolled. The main outcome was the development of CKD stage 3 or greater. The patients were divided into four groups according to the quartiles of the total serum bilirubin levels at baseline.ResultsThe group with the lowest range of total serum bilirubin level (Q1) showed the highest cumulative incidence of CKD stage 3 or greater than that of the other lower quartiles (Q1 vs. Q4; hazard ratio [HR], 6.75; 95% confidence interval [CI], 1.54 to 29.47; p = 0.011). In multivariate analysis, the risk of developing CKD stage 3 or greater was higher in the second lowest quartile of the serum bilirubin level than that in the highest quartile of the serum bilirubin level (Q2 vs. Q4; HR, 9.36; 95% CI, 1.33 to 65.73; p = 0.024). In the normoalbuminuria subgroup (n = 236), multivariate analysis showed that the risk of developing CKD stage 3 or greater was higher in the lowest quartile of the serum bilirubin level than that in the highest quartile of the serum bilirubin level (Q1 vs. Q4; HR, 7.36; 95% CI, 1.24 to 35.82; p = 0.019).ConclusionsSerum bilirubin might be an early clinical marker for predicting the progression of CKD in patients with T2DM and preserved renal function.

Urine clusterin/apolipoprotein J is linked to tubular damageand renal outcomes in patients with type 2 diabetesmellitus.

The objective of this study was to evaluate the association of urine clusterin/apolipoprotein J (Apo J) with the development and/or progression of diabetic kidney disease (DKD) in type 2 diabetes. A total of 159 type 2 diabetic patients and 20 nondiabetic subjects with estimated glomerular filtration rate (eGFR) ≥60mL/min/1.73m2 were enrolled. The baseline values of urine clusterin and tubular damage markers were measured. The primary outcome was the annual decline rate in eGFR, and secondary outcomes were the development of chronic kidney disease (CKD) stage 3 or greater and the persistence/progression of albuminuria. The median follow-up duration of enrolled patients was 3.0 (1.0-5.9) years. Baseline clusterin levels in urine were significantly increased in type 2 diabetic subjects compared with those of nondiabetic subjects. The levels of urine clusterin had a significant correlation with urine tubular damage markers. A positive correlation between the annual rate of decline in eGFR and urine clusterin after adjusting for clinical confounding factors was detected. Multivariate analysis further indicated that urine clusterin correlated with the development of CKD stage 3 or greater and persistence/progression of albuminuria. In type 2 diabetic subjects with albuminuria, urine clusterin remained associated with the annual decline rate in eGFR and the progression of CKD stage. Urine clusterin reflects tubular damage in the early stage of DKD. The increase in urine clusterin along with albuminuria could be an independent predictive marker for the progression of DKD in type 2 diabetes.

Long-term renal prognosis of cardio-renal syndrome type 1

Objectives To study the relation of acute kidney injury (AKI) and long-term chronic kidney disease (CKD) in patients with acute decompensated heart failure (ADHF). Methods The in-hospital and post-hospital clinical data of patients with ADHF were analyzed postoperatively. The AKI was diagnosed according to the KGIGO criteria, the estimated glomerular filtration rate was calculated based on serum creatinine value and the CKD was defined as an eGFR<60 mL·(min·1.73 m2)-1. Results Totally 318 patients were included. At 36 months after discharge, the decreased eGFR of 9.2% [95% confidential interval (CI) 5.9~13.0] in the AKI group was higher than the decreased eGFR of 3.8% (95% CI 1.15~5.52) in the non-AKI group. In multivariate Cox hazard ratio models, the hazard ratio (HR) of development of CKD stage was 3.012 (95% CI 1.917~4.305) in the patients with CKD at baseline, 1.849 (95% CI 1.205~2.395) in those without CKD at baseline and 1.975 (95% CI 1.213~2.435) in all the 318 patients. Conclusions The in-hospital AKI is an independent risk factor for long-term CKD development or progression, implicating the importance of long-term renal function in the patients with cardio-renal syndrome type 1. Key words: Kidney Diseases; Heart Failure; Syndrome; Prognosis

Association between copeptin and declining glomerular filtration rate in people with newly diagnosed diabetes. The Skaraborg Diabetes Register

AimsCopeptin has shown association with development of chronic kidney disease (CKD) in people with diabetes. Early detection of individuals having the highest risk could help avoid this complication. Therefore we decided to study copeptin concentrations and estimated glomerular filtration rate (eGFR) retrospectively in people with newly diagnosed diabetes. MethodsPeople with newly diagnosed type 2 diabetes in 1996–1998 from Skaraborg Diabetes Register (SDR) were reinvestigated in 2008–2010. Copeptin concentration at the time of diagnosis was determined. Creatinine and cystatin C were used for determination of eGFR at baseline and at reinvestigation (n=161). Data on cardiovascular complications were extracted from national registers. Analyzes were done with logistic regression. ResultsFrom baseline to follow up eGFR decreased with 33ml. Twenty-nine individuals (18.1%) developed CKD stage 3. There was a significant association between elevated copeptin concentrations and development of CKD stage 3 (OR=1.78, 95% CI=1.01–3.16). When adjusting for GFR at baseline the association between copeptin and GFR decline was borderline significant (OR=1.79, 95% CI=0.99–3.25, p=0.055). ConclusionsDetermination of copeptin may early identify people with diabetes and high risk for CKD. To prevent complications for these individuals aggressive treatment should be discussed.

Soluble interleukin-2 receptor alfa predicts renal outcome in IgA nephropathy

Both systemic and mucosal IgA production are controlled by T lymphocytes and infiltrating T lymphocytes are involved in the progression of interstitial fibrosis in chronic kidney disease (CKD). Since the concentration of soluble interleukin-2 receptor alfa (sIL-2Ra) reflects the degree of T cell activation over time, we studied the impact of interleukin-2 receptor alfa levels on disease progression in patients with biopsy-proven IgA nephropathy (IgAN), a disease in which 20-30% of the patients progress to end-stage renal failure. sIL-2Ra plasma levels were measured in 194 patients (median age 39 years, 70% men) and 84 matched controls. One hundred and seventy-nine of the patients, with an estimated glomerular filtration rate (GFR) of ≥15 mL/min/1.73m(2) at baseline (CKD Stages 1-4), were followed for up to 15 years (median 52 months; range 12-188). sIL-2Ra was evaluated as a risk marker for severe renal progression, here defined by the development of CKD Stage 5 (GFR <15 mL/min/1.73m(2)), a 50% decline in GFR during the follow-up period or a 30% GFR decline within 5 years of follow-up. In 51 patients, upon whom a renal biopsy had been performed within 2 years of IL2-Ra measurement, the biopsies were scored according to the Oxford classification. The correlations between the histopathological findings and the sIL-2Ra levels were examined. sIL2-Ra levels were significantly higher in patients than in controls (P < 0.001). sIL-2Ra levels in the upper third tertile predicted a severe renal outcome, even after adjustment for the main clinical risk factors: time average albuminuria and GFR at baseline (Relative risk 5.35, P < 0.001). sIL-2Ra levels also correlated significantly to the yearly GFR slope (β = -0.24, P = 0.01). According to the Oxford classification, the presence of >25% tubular atrophy/interstitial fibrosis (T1-2) was associated with higher sIL-2Ra levels, after adjustment for serum creatinine levels, if analysed within 4 months [n = 24, odds ratio (OR) 1.0, P = 0.044] or within 2 years from the kidney biopsy (n = 51, OR 1.0, P = 0.017). The plasma levels of sIL-2Ra were predictive of long-term renal disease progression in a large cohort of patients with biopsy-proven IgAN. Further studies are warranted to evaluate if sIL-2Ra levels can feasibly contribute in the monitoring of effects of treatment, aimed to prevent the progression of interstitial fibrosis and progressive glomerulosclerosis in IgAN.

Impact of implementation of the MELD scoring system on the prevalence and incidence of chronic renal disease following liver transplantation

Impact of implementation of the MELD scoring system on the prevalence and incidence of chronic renal disease following liver transplantation