Summary The global nephrology community recognises the need for a cohesive plan to address the problem of chronic kidney disease (CKD). In July, 2016, the International Society of Nephrology hosted a ...CKD summit of more than 85 people with diverse expertise and professional backgrounds from around the globe. The purpose was to identify and prioritise key activities for the next 5–10 years in the domains of clinical care, research, and advocacy and to create an action plan and performance framework based on ten themes: strengthen CKD surveillance; tackle major risk factors for CKD; reduce acute kidney injury—a special risk factor for CKD; enhance understanding of the genetic causes of CKD; establish better diagnostic methods in CKD; improve understanding of the natural course of CKD; assess and implement established treatment options in patients with CKD; improve management of symptoms and complications of CKD; develop novel therapeutic interventions to slow CKD progression and reduce CKD complications; and increase the quantity and quality of clinical trials in CKD. Each group produced a prioritised list of goals, activities, and a set of key deliverable objectives for each of the themes. The intended users of this action plan are clinicians, patients, scientists, industry partners, governments, and advocacy organisations. Implementation of this integrated comprehensive plan will benefit people who are at risk for or affected by CKD worldwide.
Recent studies suggest that alkalinizing treatments improve the course of chronic kidney disease (CKD), even in patients without overt metabolic acidosis. Here, we tested whether a decreased ability ...in excreting urinary acid rather than overt metabolic acidosis may be deleterious to the course of CKD. We studied the associations between baseline venous total CO2 concentration or urinary ammonia excretion and long-term CKD outcomes in 1065 patients of the NephroTest cohort with CKD stages 1–4. All patients had measured glomerular filtration rate (mGFR) by 51Cr-EDTA renal clearance. Median mGFR at baseline was 37.6 ml/min per 1.73 m2. Urinary ammonia excretion decreased with GFR, whereas net endogenous acid production did not. After a median follow-up of 4.3 years, 201 patients reached end-stage renal disease (ESRD) and 114 died before ESRD. Twenty-six percent of the patients had mGFR decline rate greater than 10% per year. Compared with patients in the highest tertile of urinary ammonia excretion, those in the lowest tertile had a significantly increased hazard ratio for ESRD, 1.82 (95% CI, 1.06–3.13), and a higher odds ratio of fast mGFR decline, 1.84 (0.98–3.48), independent of mGFR and other confounders. Patients in the lowest tertile of venous total CO2 had significantly increased risk of fast mGFR decline but not of ESRD. None of these biomarkers was associated with mortality. Thus, these results suggest that the inability to excrete the daily acid load is deleterious to renal outcomes.
Membranous Nephropathy (MN) is a rare autoimmune cause of kidney failure. Here we report a genome-wide association study (GWAS) for primary MN in 3,782 cases and 9,038 controls of East Asian and ...European ancestries. We discover two previously unreported loci, NFKB1 (rs230540, OR = 1.25, P = 3.4 × 10
) and IRF4 (rs9405192, OR = 1.29, P = 1.4 × 10
), fine-map the PLA2R1 locus (rs17831251, OR = 2.25, P = 4.7 × 10
) and report ancestry-specific effects of three classical HLA alleles: DRB1*1501 in East Asians (OR = 3.81, P = 2.0 × 10
), DQA1*0501 in Europeans (OR = 2.88, P = 5.7 × 10
), and DRB1*0301 in both ethnicities (OR = 3.50, P = 9.2 × 10
and OR = 3.39, P = 5.2 × 10
, respectively). GWAS loci explain 32% of disease risk in East Asians and 25% in Europeans, and correctly re-classify 20-37% of the cases in validation cohorts that are antibody-negative by the serum anti-PLA2R ELISA diagnostic test. Our findings highlight an unusual genetic architecture of MN, with four loci and their interactions accounting for nearly one-third of the disease risk.
Summary Background Hypertension is the most prevalent comorbidity in individuals with chronic kidney disease. However, whether the association of the kidney disease measures, estimated glomerular ...filtration rate (eGFR) and albuminuria, with mortality or end-stage renal disease (ESRD) differs by hypertensive status is unknown. Methods We did a meta-analysis of studies selected according to Chronic Kidney Disease Prognosis Consortium criteria. Data transfer and analyses were done between March, 2011, and June, 2012. We used Cox proportional hazards models to estimate the hazard ratios (HR) of mortality and ESRD associated with eGFR and albuminuria in individuals with and without hypertension. Findings We analysed data for 45 cohorts (25 general population, seven high-risk, and 13 chronic kidney disease) with 1 127 656 participants, 364 344 of whom had hypertension. Low eGFR and high albuminuria were associated with mortality irrespective of hypertensive status in the general population and high-risk cohorts. All-cause mortality risk was 1·1–1·2 times higher in individuals with hypertension than in those without hypertension at preserved eGFR. A steeper relative risk gradient in individuals without hypertension than in those with hypertension at eGFR range 45–75 mL/min per 1·73 m2 led to much the same mortality risk at lower eGFR. With a reference eGFR of 95 mL/min per 1·73 m2 in each group to explicitly assess interaction, adjusted HR for all-cause mortality at eGFR 45 mL/min per 1·73 m2 was 1·77 (95% CI 1·57–1·99) in individuals without hypertension versus 1·24 (1·11–1·39) in those with hypertension (p for overall interaction=0·0003). Similarly, for albumin-creatinine ratio of 300 mg/g ( vs 5 mg/g), HR was 2·30 (1·98–2·68) in individuals without hypertension versus 2·08 (1·84–2·35) in those with hypertension (p for overall interaction=0·019). We recorded much the same results for cardiovascular mortality. The associations of eGFR and albuminuria with ESRD, however, did not differ by hypertensive status. Results for chronic kidney disease cohorts were similar to those for general and high-risk population cohorts. Interpretation Chronic kidney disease should be regarded as at least an equally relevant risk factor for mortality and ESRD in individuals without hypertension as it is in those with hypertension. Funding US National Kidney Foundation.
We performed a genome-wide association study (GWAS) of IgA nephropathy (IgAN), the most common form of glomerulonephritis, with discovery and follow-up in 20,612 individuals of European and East ...Asian ancestry. We identified six new genome-wide significant associations, four in ITGAM-ITGAX, VAV3 and CARD9 and two new independent signals at HLA-DQB1 and DEFA. We replicated the nine previously reported signals, including known SNPs in the HLA-DQB1 and DEFA loci. The cumulative burden of risk alleles is strongly associated with age at disease onset. Most loci are either directly associated with risk of inflammatory bowel disease (IBD) or maintenance of the intestinal epithelial barrier and response to mucosal pathogens. The geospatial distribution of risk alleles is highly suggestive of multi-locus adaptation, and genetic risk correlates strongly with variation in local pathogens, particularly helminth diversity, suggesting a possible role for host-intestinal pathogen interactions in shaping the genetic landscape of IgAN.
The established chronic kidney disease (CKD) progression end point of end-stage renal disease (ESRD) or a doubling of serum creatinine concentration (corresponding to a change in estimated glomerular ...filtration rate GFR of −57% or greater) is a late event.
To characterize the association of decline in estimated GFR with subsequent progression to ESRD with implications for using lesser declines in estimated GFR as potential alternative end points for CKD progression. Because most people with CKD die before reaching ESRD, mortality risk also was investigated.
Individual meta-analysis of 1.7 million participants with 12,344 ESRD events and 223,944 deaths from 35 cohorts in the CKD Prognosis Consortium with a repeated measure of serum creatinine concentration over 1 to 3 years and outcome data.
Transfer of individual participant data or standardized analysis of outputs for random-effects meta-analysis conducted between July 2012 and September 2013, with baseline estimated GFR values collected from 1975 through 2012.
End-stage renal disease (initiation of dialysis or transplantation) or all-cause mortality risk related to percentage change in estimated GFR over 2 years, adjusted for potential confounders and first estimated GFR.
The adjusted hazard ratios (HRs) of ESRD and mortality were higher with larger estimated GFR decline. Among participants with baseline estimated GFR of less than 60 mL/min/1.73 m2, the adjusted HRs for ESRD were 32.1 (95% CI, 22.3-46.3) for changes of −57% in estimated GFR and 5.4 (95% CI, 4.5-6.4) for changes of −30%. However, changes of −30% or greater (6.9% 95% CI, 6.4%-7.4% of the entire consortium) were more common than changes of −57% (0.79% 95% CI, 0.52%-1.06%). This association was strong and consistent across the length of the baseline period (1 to 3 years), baseline estimated GFR, age, diabetes status, or albuminuria. Average adjusted 10-year risk of ESRD (in patients with a baseline estimated GFR of 35 mL/min/1.73 m2) was 99% (95% CI, 95%-100%) for estimated GFR change of −57%, was 83% (95% CI, 71%-93%) for estimated GFR change of −40%, and was 64% (95% CI, 52%-77%) for estimated GFR change of −30% vs 18% (95% CI, 15%-22%) for estimated GFR change of 0%. Corresponding mortality risks were 77% (95% CI, 71%-82%), 60% (95% CI, 56%-63%), and 50% (95% CI, 47%-52%) vs 32% (95% CI, 31%-33%), showing a similar but weaker pattern.
Declines in estimated GFR smaller than a doubling of serum creatinine concentration occurred more commonly and were strongly and consistently associated with the risk of ESRD and mortality, supporting consideration of lesser declines in estimated GFR (such as a 30% reduction over 2 years) as an alternative end point for CKD progression.
Summary Resistant hypertension is defined as blood pressure above goal despite adherence to a combination of at least three optimally dosed antihypertensive medications, one of which is a diuretic. ...Chronic kidney disease is the most frequent of several patient factors or comorbidities associated with resistant hypertension. The prevalence of resistant hypertension is increased in patients with chronic kidney disease, while chronic kidney disease is associated with an impaired prognosis in patients with resistant hypertension. Recommended low-salt diet and triple antihypertensive drug regimens that include a diuretic, should be complemented by the sequential addition of other antihypertensive drugs. New therapeutic innovations for resistant hypertension, such as renal denervation and carotid barostimulation, are under investigation especially in patients with advanced chronic kidney disease. We discuss resistant hypertension in chronic kidney disease stages 3–5 (ie, patients with an estimated glomerular filtration rate below 60 mL/min per 1·73 m2 and not on dialysis), in terms of worldwide epidemiology, outcomes, causes and pathophysiology, evidence-based treatment, and a call for action.
Timing of Onset of CKD-Related Metabolic Complications MORANNE, Olivier; FROISSART, Marc; FOUQUERAY, Bruno ...
Journal of the American Society of Nephrology,
2009, 2009-Jan, 2009-01-00, 20090101, 2009-01, Volume:
20, Issue:
1
Journal Article
Peer reviewed
Open access
Chronic kidney disease (CKD) guidelines recommend evaluating patients with GFR <60 ml/min per 1.73 m(2) for complications, but little evidence supports the use of a single GFR threshold for all ...metabolic disorders. We used data from the NephroTest cohort, including 1038 adult patients who had stages 2 through 5 CKD and were not on dialysis, to study the occurrence of metabolic complications. GFR was measured using renal clearance of (51)Cr-EDTA (mGFR) and estimated using two equations derived from the Modification of Diet in Renal Disease study. As mGFR decreased from 60 to 90 to <20 ml/min per 1.73 m(2), the prevalence of hyperparathyroidism increased from 17 to 85%, anemia from 8 to 41%, hyperphosphatemia from 1 to 30%, metabolic acidosis from 2 to 39%, and hyperkalemia from 2 to 42%. Factors most strongly associated with metabolic complications, independent of mGFR, were younger age for acidosis and hyperphosphatemia, presence of diabetes for acidosis, diabetic kidney disease for anemia, and both male gender and the use of inhibitors of the renin-angiotensin system for hyperkalemia. mGFR thresholds for detecting complications with 90% sensitivity were 50, 44, 40, 39, and 37 ml/min per 1.73 m(2) for hyperparathyroidism, anemia, acidosis, hyperkalemia, and hyperphosphatemia, respectively. Analysis using estimated GFR produced similar results. In summary, this study describes the onset of CKD-related complications at different levels of GFR; anemia and hyperparathyroidism occur earlier than acidosis, hyperkalemia, and hyperphosphatemia.
Among patients on hemodialysis, pruritus has been associated with poorer mental and physical quality of life, sleep quality, depression, and mortality. We evaluated patients with nondialysis CKD to ...describe the prevalence of pruritus, identify associated factors, and investigate associations with patient-reported outcomes.
Using cross-sectional data from patient questionnaires in the CKD Outcomes and Practice Patterns Study (CKDopps), we asked patients with CKD stages 3-5 (nondialysis) from the United States, Brazil, and France to identify how much they were bothered by pruritus. Response options ranged from "not at all" to "extremely." Log-Poisson regression, yielding prevalence ratios, was used to evaluate associations of moderate-to-extreme pruritus with patient characteristics, CKD stage, self-reported depression symptoms, and restless sleep. Mixed linear regression was used to examine associations between pruritus and physical and mental component summary scores, with lower scores indicating poorer quality of life.
Of the 5658 CKDopps patients enrolled in the United States, Brazil, and France, 3780 (67%) answered the pruritus question. The prevalence of moderate-to-extreme pruritus was 24%, and more likely in older patients, women, and those with stage 5 CKD, lung disease, diabetes, and physician-diagnosed depression. In adjusted models, patients with moderate pruritus had physical and mental component summary scores 3.5 (95% confidence interval 95% CI, -4.6 to -2.3) and 2.3 (95% CI, -3.2 to -1.5) points lower, respectively, than patients without pruritus, and they also had a higher adjusted prevalence of patient-reported depression (prevalence ratio, 1.83; 95% CI, 1.58 to 2.11) and restless sleep (prevalence ratio, 1.69; 95% CI, 1.49 to 1.91) compared with patients without pruritus. These patient-reported outcomes were progressively worse with increasing severity of pruritus.
Our findings demonstrate high prevalence of pruritus in nondialysis CKD, as well as strong associations of pruritus with poor health-related quality of life, self-reported depression symptoms, and self-reported poor sleep.
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