Progression Of Renal Insufficiency Research Articles

Phosphate Toxicity and Vascular Calcification in Chronic Kidney Disease: A Closer Look Utilizing Transmission Electron Microscopy.

Hyperphosphatemia is independently linked with vascular calcification, cardiovascular disease, bone-mineral disease, progression of renal insufficiency, and all-cause mortality in chronic kidney disease (CKD) and end-stage renal disease (ESRD). The emerging importance of fibroblast growth factor-23 (FGF-23) and its co-factor Klotho play very important roles as phosphaturic hormones; however, phosphate levels rise due to a loss of renal Klotho production and the phosphaturic effects of the FGF-23/Klotho axis. Hyperphosphatemia is also associated with calciphylaxis, acceleration of renal tubulointerstitial disease, renal osteodystrophy, and uremic cardiomyopathy. This review incorporates ultrastructural remodeling of the thoracic aorta to provide a different perspective on vascular calcification. Nine-week-old male heterozygous (mRen2) 27 (Ren2) rat models of hypertension, insulin resistance, vascular oxidative stress and albuminuria are utilized to demonstrate aortic remodeling associated with vascular calcification. Nine-week-old male Zucker obese (fa/fa) rat models are utilized to better understand nephrolith formation. Phosphate homeostasis, toxicity, multiple metabolic and uremic toxicities, renal osteodystrophy, and vascular calcification are also discussed. Additionally, the role of the endothelium, vascular smooth muscle cells, inflammatory monocytes/macrophages and mast cells, pericytes, oxidative stress, hydrogen sulfide, and extraosseous calcification in the kidney are discussed as they relate to CKD, ESRD and calciphylaxis.

Blood pressure goals in chronic kidney disease : What is the optimal blood pressure for inhibition of progression and risk reduction?

Well-controlled blood pressure is an essential factor in inhibiting the progression of renal failure and also in controlling cardiovascular mortality and morbidity. For decades there has been an intensive search for the optimal blood pressure target values in order to reduce the progression of renal insufficiency to aphysiological level as far as possible. In the last few decades, very different target blood pressure values have been defined, which time and again contribute more to confusion than clarity in everyday clinical practice. The present work considers the relevant guidelines; it analyzes the basis on which the sometimes widely varying guidelines were created. All guidelines agree that blood pressure control with atarget of less than 140 mm Hg systolic should be achieved in patients with impaired renal function. The European guidelines recommend aiming for atarget of 130-140 mm Hg systolic. The American guidelines go one step further and specify asystolic blood pressure target of less than 130 mm Hg. The Kidney Disease: Improving Global Outcomes (KDIGO) organization is even more ambitious. It recommends ablood pressure target of less than 120 mm Hg, whereby in contrast to the European and American guidelines, the level of evidence required in the guidelines is considered to be very weak and the goals should also be achieved if automated, standardized blood pressure measurement is carried out, which is rarely available in everyday practice and may not be feasible. The present overview discusses the arguments for lowering blood pressure with different goals and presents the evidence. Of course, the blood pressure goals in the presence or absence of albuminuria should also be considered.

Current options for slowing the progression of chronic kidney disease.

From a certain stage, chronic kidney disease progresses to terminal kidney failure that requires renal replacement therapy with dialysis or transplantation. The progression can be significantly slowed by blocking the renin angiotensin aldosterone system (RAAS) with angiotensin converting enzyme (ACE) inhibitors or angiotensin II type 1 receptor blockers (ARB). Another new option to enhance the effect of blocking the RAAS system is the use of sodium glucose cotransporter 2 (SGLT2) inhibitors, or gliflozins. Dapagliflozin is currently available and reimbursed for patients with both diabetic and non-diabetic kidney disease. In the near future, treatment with the mineralocorticoid receptor inhibitor finerenone should be made available that significantly potentiates the effect of ACE or ARB inhibitors. Recent data show that it is possible to influence the progression of renal insufficiency with exercise.

Clinical and pathologic analysis of kidney damage in patients with nephrotic syndrome in the Republic of Srpska

Background / Aim: Nephrotic syndrome (NS) is a clinical syndrome characterised by massive proteinuria > 3.5 g in 24 h urine, hypoalbuminaemia, hyperlipidaemia and oedema. Aim of this study was to determine the aetiology and frequency of kidney diseases that occur as the cause of NS in adults in the Republic of Srpska and the progression of renal insufficiency, disease outcomes and efficacy of applied therapy. Methods: The retrospective study included patients aged 18 to 80 hospitalised between 2014 and 2018 due to clinically and laboratory-manifested NS. In patients with suspected primary glomerular disease, a kidney biopsy with immunofluorescent dyeing was performed. The first examination involved hospital admission and the next check-up six months after the first hospitalisation. Basic clinical parameters were followed: creatinine, clearance creatinine, albumin, total protein, cholesterol, total protein in 24 h urine and microscopy of urine during the first hospitalisation and repeated same laboratory findings on control. The progression of kidney failure during this period was assessed, as well as the efficacy of immunosuppressive therapy. Results: In primary NS category membranous glomerulonephritis (MGN) was present at 40.7 % of patients, followed by focal segmental glomerulosclerosis (FSGS) 21.7 %, membranoproliferative glomerulonephritis (MPGN) 11.9 % and IgA glomerulonephritis (IgAN) 11.9 %. Nephroangiosclerosis was verified as the most common cause of secondary NS with 28.8 % and lupus nephritis 21.2 %, followed by ANCA-associated GN (11.5 %) and diabetic nephropathy (11.5 %). Thirty-four patients (21 %) died during the follow-up. Thirty-four patients (18.6 %) progressed to end stage renal disease during the five-year follow-up. Conclusion: The pathology of kidney disease in older patients is often very complex; therefore, a kidney biopsy should be conducted at an early stage of kidney disease for the purpose of obtaining an accurate diagnosis, determining appropriate treatment and thus improving the prognosis of the patient.

Clinical and Pathological Characteristics of Patients With Nonproteinuric Diabetic Nephropathy.

IntroductionAs the most common complication of diabetes mellitus (DM), diabetic nephropathy (DN) was initially considered to begin with proteinuria preceding the progression of renal insufficiency. This clinical paradigm has been questioned in the late decades, as many DM patients without proteinuria have progressive renal insufficiency. However, the characteristics of nonproteinuric DN were not fully clear yet.Patients and MethodsA total of 390 patients with renal biopsy-proven DN in our center were retrospectively recruited in the current study. Clinical and histopathological data of the patients were analyzed. We used propensity score-matching methods to address the imbalance of age, sex, and diabetes duration for comparative analyses.ResultsAmong all the renal biopsy-proven DN patients with renal biopsy proven DN, 18 patients were classified as nonproteinuric DN. Compared with 36 propensity score-matched proteinuric DN patients, diabetic retinopathy (DR) was less frequent in nonproteinuric DN patients (38.9% vs. 66.4%, p<0.05). During the follow-up of 24.0 (12.0–42.0) months, the probability of developing the end-stage renal disease (ESRD) was significantly lower in nonproteinuric DN patients than in proteinuric ones in both the propensity score-matched cohort and overall cohort (log-rank test, p<0.001 and p<0.001, respectively).ConclusionsCompared with proteinuric DN patients, DR was less frequent in nonproteinuric DN patients. Nonproteinuric DN patients had better renal outcomes than proteinuric DN patients.

The Influence of Dietary Interventions on Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD).

Chronic kidney disease is a health problem whose prevalence is increasing worldwide. The kidney plays an important role in the metabolism of minerals and bone health and therefore, even at the early stages of CKD, disturbances in bone metabolism are observed. In the course of CKD, various bone turnover or mineralization disturbances can develop including adynamic hyperparathyroid, mixed renal bone disease, osteomalacia. The increased risk of fragility fractures is present at any age in these patients. Nutritional treatment of patients with advanced stages of CKD is aiming at prevention or correction of signs, symptoms of renal failure, avoidance of protein-energy wasting (PEW), delaying or prevention of the occurrence of mineral/bone disturbances, and delaying the start of dialysis. The results of studies suggest that progressive protein restriction is beneficial with the progression of renal insufficiency; however, other aspects of dietary management of CKD patients, including changes in sodium, phosphorus, and energy intake, as well as the source of protein and lipids (animal or plant origin) should also be considered carefully. Energy intake must cover patients’ energy requirement, in order to enable correct metabolic adaptation in the course of protein-restricted regimens and prevent negative nitrogen balance and protein-energy wasting.

Multidisciplinary Team Care Delays the Initiation of Renal Replacement Therapy in Diabetes: A Five-year Prospective, Single-center Study

Objective Although recent reports have highlighted the benefits of multidisciplinary team care (MTC) for chronic kidney disease (CKD) in slowing the progress of renal insufficiency, its long-term effects have not been evaluated for patients with diabetes mellitus (DM). We compared the renal survival rate between MTC and conservative care (CC). Methods In this five-year, single-center, prospective, observational study, we examined 24 patients (mean age 65.5±12.1 years old, men/women 18/6) with DM-induced CKD stage ≥3 in an MTC clinic. The control group included 24 random patients with DM (mean age 61.0±12.8 years old, men/women 22/2) who received CC. MTC was provided by a nephrologist and medical staff, and CC was provided by a nephrologist. Results In total, 10 MTC and 20 CC patients experienced renal events [creatinine doubling, initiation of renal replacement therapy (RRT), or death due to end-stage CKD]. During the five-year observation period, there were significantly fewer renal events in the MTC group than in the CC group according to the cumulative incidence method (p=0.006). Compared to CC, MTC significantly reduced the need for urgent initiation of hemodialysis (relative risk reduction 0.79, 95% confidence interval [CI] 0.107-0.964). On a multivariate analysis, MTC (hazard ratio [HR], 0.434, 95% CI 0.200-0.939) and the slope of the estimated glomerular filtration rate during the first year (HR, 0.429 per 1 mL/min/m2/year, 95% CI 0.279-0.661) were negatively associated with renal events. Conclusion MTC for DM-induced CKD is an effective strategy for delaying RRT. Long-term MTC can demonstrate reno-protective effects.

Workplace Screening Identifies Clinically Significant and Potentially Reversible Kidney Injury in Heat-Exposed Sugarcane Workers.

An epidemic of chronic kidney disease of unknown origin (CKDu) has emerged in the past two decades in agricultural communities, characterized by progressive renal failure with a dearth of early clinical symptoms. The aim of this study is to improve understanding of the natural history of this disease and to evaluate the impact of an educational and behavioral intervention on the trajectories of renal decline among a cohort of Guatemalan sugarcane workers. We identified groups of workers based on their kidney function during a longitudinal parent study conducted among sugarcane workers during the 2016–2017 harvest season. At the study’s first time point in February 2017, workers who developed abnormal kidney function (AKF) (estimated glomerular filtration rate, eGFR, <60 mL/min per 1.73 m2) were placed in the AKF group, workers with reduced kidney function (RKF) (eGFR 60–89) were placed in the RKF group, and workers who maintained normal kidney function (NKF) (eGFR ≥ 90) were placed in the NKF group. As part of the study, a health promotion, behavioral and educational intervention centered on water, electrolytes, rest, and shade (WERS) was provided to all study participants. We then prospectively analyzed renal function at the three study time points in February, March, and April. Additional data collected from previous harvests allowed for retrospective analysis and we compared the rate of change in eGFR over the previous five years (2012 to 2016) for each identified group. Mixed effects linear regression with random intercepts for the workers was used to investigate the difference in rates of change for the three groups and to assess the impact of the intervention study on rate of change of kidney function during the study compared to each group’s prior trajectory, utilizing the retrospective data collected during the five years prior to the study intervention. Between 2012 and 2016, eGFR declined at a rate of 0.18 mL/min per 1.73 m2 per year for the NKF group (95% CI: −0.66, 0.29, p = 0.45), 2.02 per year for the RKF group (95% CI: 1.00, 3.03, p = 0.0001) and 7.52 per year for the AKF group (95% CI: 6.01, 9.04, p < 0.0001). All study groups stabilized or improved their trajectory of decline during the intervention. This study supports the need to institute WERS interventions and to include mid-harvest screening protocols and longitudinal tracking of kidney function among sugarcane workers at high risk of CKDu. Early detection of rapid kidney function decline combined with appropriate interventions hold promise for stopping or slowing progression of renal insufficiency among these workers.

P0756THE RELATIONSHIP BETWEEN ABDOMINAL AORTIC CALCIFICATION AND PROGRESSION OF RENAL INSUFFICIENCY IN PATIENTS WITH CHRONIC KIDNEY DISEASE

Abstract Background and Aims Although abdominal aortic calcification (AAC) is known to be associated with cardiovascular mortality in patients with chronic kidney disease (CKD), there are little information about the impact of AAC on progression of CKD. Therefore, we investigated the relationship between the AAC and progression of renal insufficiency in CKD patients with early stage. Method A total of 183 patients with CKD, stage 3 was included. The degree of AAC was evaluated by computed tomography and the score was calculated as follows: abdominal calcification index (ACI)= (total score of calcification on all slices)/12 × 1/(number of slices) × 100%. Based on tertile of ACI, the patients were divided into three groups: low-, intermediate-, and high-groups. The annual decline of glomerular filtration rate (GFR) and time to dialysis were assessed. Results The AAC was found (ACI &amp;gt; 0) in 129 patients (70.4%), and the mean ACI was 21.3 %. The average duration of follow-up was 46.9 months. The high ACI group showed higher annual decline in GFR compared to other groups (27.8 vs 14.5 vs 11.3 mL/min, p=0.042). During the follow-up, 68.8% (42/61) of high ACI group received dialysis and the time to dialysis was significantly shorter than other groups (14.8 vs. 25.8 vs.29.1 months, p=0.038) Conclusion In this study, we showed the AAC was associated with rapid progression of CKD. Evaluation of the AAC in CKD with early stage provides useful information for predicting the progression of CKD.

P0427IGA GLOMERULONEPHRITIS WITH MASSIVE PROTEINURIA- CASE SERIES WITH CLINICAL AND PATHOHISTOLOGICAL REVIEW

Abstract Background and Aims IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide. The classic manifestation of IgAN is episodic hematuria and proteinuria. Nephrotic syndrome (NS) is not common in IgAN. It is reported to occur in 5-10% of patients with IgAN. Clinical presentation with massive proteinuria is exceptional. Method We retrospectively analyzed patients with pathohistologically proven IgAN who initially presented with 24h proteinuria greater than 10 gr. Here we presented their clinical, biochemical and pathohistological (electron microscopy-EM, was provided in all cases) characteristics with clinical outcomes. Data were taken from Renal biopsy Registry of Department of Nephrology Dubrava University hospital. Results All together 12 patients (10 M, 2 F) average age 53 (range 25-81) years were included. This represents 3,2% of all IgAN patients in our Renal biopsy Registry (presently there are more than 2100 patients in total, 366 with IgAN). Arterial hypertension had 10 out of 12 patients and three patients had diabetes mellitus type 2. Other significant comorbidities included lung adenocarcinoma in one patient, history of preeclampsia, mitral valve replacement surgery and liver cirrhosis, each in one patient. Average serum creatinine level at presentation was 223,9 (90-549) µmol/L and average 24h proteinuria was 14,6 (10,2-32) gr. All patients had haematuria. Renal insufficiency was found in 7 patients and additionally in two patients rapidoprogressive clinical pattern was recognized. Oxford classification was applied for all patients. In all except one, mesangial hypercellularity (M1) was found, endocapillary proliferation (E1) in 4 and cellular crescents in 5 patients (C1 in 4, C2 in 1 patient). The average percentage of globally sclerosing glomeruli was 32% (10-85%) and IFTA was 33% (10-60%), respectively. On EM diffuse podocyte foot processes effacement was documented only in two patients. In patients with diabetes mellitus there were not signs of diabetic nephropathy (i.e. thickened GBM on EM). Two patients who presented with purpuric rash and arthritis were considered to have IgA vasculitis (Henoch Schoenlein purpura). Considering treatment, glucocorticosteroids and RAAS blockators (apart from those who were dialysis dependent) were introduced. Five patients were also treated with cyclophosphamide. Average time of follow-up was 53 months (2-156). Regarding clinical outcomes, 4 patients achieved remission (2 partial and 2 complete). One of those experienced clinical relaps and underwent kidney rebiosy. In one patient stationary course and in another one progression of renal insufficiency were noted. Both patients diagnosed as IgA vasculitis were dialysis depended at presentation and during follow-up period unfortunately died. Two more patients died latter on as a consequence of a non-renal disorders. One more patient who developed ESRD was transplanted but afterwards he rejected the graft. One patient was lost from follow-up. Conclusion Proteinuria is well known independent progression risk factor in IgAN. In presented study we showed that almost one third of IgAN patients who manifested with massive proteinuria ended up in ESRD in relatively short follow-up period.

A Novel Genetically Defined Mouse Model of Hypertensive Nephropathy

The molecular pathways that drive hypertensive nephropathy remain poorly understood. Hypertension (HTN) and chronic kidney disease are comorbid disorders with a correlation as high as 70% in African‐Americans over 65 years old. Because impaired kidney function can be the cause or consequence of HTN, identification of causal hypertensive nephropathy pathways has been especially difficult. Here, we overcome the roadblock with a new genetically‐defined mouse model of HTN that exhibit a low‐renin salt‐sensitive form of the disease, similar to HTN in individuals of sub‐Saharan African descent. The mice, created by introducing activating mutations in the Ste20p‐related proline alanine‐rich kinase (SPAK) in a distal convoluted tubule cell‐specific manner, become hypertensive solely as a consequence of constitutive activation of the thiazide‐sensitive sodium chloride cotransporter (NCC) and salt retention.For these studies, the constitutively active (CA)‐SPAK and control (C57BL/6J) mice were fed control or high salt diet (HSD), and renal function was evaluated over 40 weeks, together with telemetric measurements of blood pressure. RNA‐Seq was performed to evaluate changes in the transcriptional profile in the renal cortex, and corroborated biochemically.Renal function in CA‐SPAK mice began to deteriorate at 20 weeks as evidenced by significant elevation of BUN, creatinine, and frank albuminuria, which gradually increased over the next 20 weeks. HSD consumption exacerbated hypertension in CA‐SPAK mice, and accelerated the decline in renal function. Microscopic evaluation of trichrome‐stained specimens revealed no significant changes in the kidney parenchyma. Thus hypertension appears to drive kidney insufficiency long before the development of nephroangiosclerosis.By contrast, a significant change in the transcription profile was observed between CA‐SPAK mice and controls at an early stage when microalbuminuria begins to develop. 1905 differentially expressed (DE) genes were identified (modified TREAT method, FDR &lt; 0.05 for genes &gt; 10% change). Remarkably, the DE profile was enriched in 26% of the known genes associated with albuminuria in humans (Chi Square test, p = 0.00031). Significant downregulation of key components of the glomerular filtration barrier slit diaphragm genes (nephrin, podocalyxin, synaptopodin, actinin a4, phospholipase C ɛ1) and the proximal tubule protein scavenger, Cubilin, were also observed in the CA‐SPAK. Pathway analysis was especially enriched in proinflammatory responses. Signature genes associated with Major Histocompatibility Complex class II, T helper 17 lymphocytes master regulator transcription factors and B lymphocytes markers were up‐regulated in the CA‐SPAK mice.In conclusion, progression of renal insufficiency in CA‐SPAK mice indicates a causal role of hypertension in nephropathy, and incriminates an inflammatory component as a key driver of early damage to the glomerular filtration barrier and tubular protein reabsorption.Support or Funding InformationThis study was supported by NIH.

The nephrology eHealth-system of the metropolitan region of Hannover for digitalization of care, establishment of decision support systems and analysis of health care quality

BackgroundEven though a high demand for sector spanning communication exists, so far no eHealth platform for nephrology is established within Germany. This leads to insufficient communication between medical providers and therefore suboptimal nephrologic care. In addition, Clinical Decision Support Systems have not been used in Nephrology until now.MethodsThe aim of NEPHRO-DIGITAL is to create a eHealth platform in the Hannover region that facilitates integrated, cross-sectoral data exchange and includes teleconsultation between outpatient nephrology, primary care, pediatricians and nephrology clinics to reduce communication deficits and prevent data loss, and to enable the creation and implementation of an interoperable clinical decision support system. This system will be based on input data from multiple sources for early identification of patients with cardiovascular comorbidity and progression of renal insufficiency. Especially patients will be able to enter and access their own data. A transfer to a second nephrology center (metropolitan region of Erlangen-Nuremburg) is included in the study to prove feasibility and scalability of the approach.DiscussionA decision support system should lead to earlier therapeutic interventions and thereby improve the prognosis of patients as well as their treatment satisfaction and quality of life. The system will be integrated in the data integration centres of two large German university medicine consortia (HiGHmed (highmed.org) and MIRACUM (miracum.org)).Trial registrationISRCTN16755335 (09.07.2019).

Association of hyperkalemia with clinical outcomes in advanced chronic kidney disease

IntroductionPatients with advanced chronic kidney disease (CKD) are at greatest risk of hyperkalemia (HK). The relationship between HK and negative outcomes (mortality or progression of renal insufficiency) in non-dialysis dependent CKD patients is controversial. AimsTo determine the incidence, prevalence, and factors related with HK in a cohort of CKD patients, and its relationship with mortality, hospitalization rate, CKD progression, and dialysis initiation. Material and methodsA retrospective, observational study in an incident cohort of adult patients with stage 4 or 5 CKD not on dialysis. Inclusion criteria were: having at least three consecutive estimated glomerular filtration rate (eGFR) measurements in a follow-up period >3 months. Decline in renal function was estimated as the slope of the individual linear regression line of eGFR over follow-up time. HK was defined as serum K levels ≥5.5meq/l. Associations of HK with outcomes were adjusted for major confounding variables in the multivariate analysis. ResultsThe study group consisted of 1079 patients (574 males, mean age: 65±14 years) with mean baseline eGFR 14.8±4.5ml/min/1.73m2. Mean follow-up time was 15 months with a median of 7 serum sample determinations per patient. HK was observed at baseline in 26% of patients; in at least one serum sample during the individual follow-up period in 68%; or chronically (>50% of samples) in 33% of patients. By multivariate logistic regression, the best determinants of chronic HK were: male sex (OR=1.529; 95% CI [1.154–2.025], p=.003), serum bicarbonate (OR=0.863 [0.829–0.900], p<.0001), diuretic treatment (OR=0.743 [0.556–0.992], p=.044), and angiotensin converting enzyme inhibitor and/or angiotensin receptor blockers (OR=4.412 [2.915–6.678], p<.0001). Patients whose serum K levels were in the upper quartile showed a significantly faster CKD progression (−4.05±5.22 vs. −2.69±5.61ml/min/1.73m2/year, p<.0001), and more frequent dialysis initiation (63% vs. 57%, p=.115), though lower mortality (9% vs. 17%, p=.003) and hospitalization rates (2.68±5.94 vs. 3.16±6.77 days per year, p=.301) than the other study patients. However, in the multivariate analysis, average serum K levels were not independently associated with the clinical outcomes investigated. ConclusionHK is a common biochemical finding in non-dialysis dependent CKD patients, mainly associated with prescribed medication. However, HK was not independently associated with major negative clinical outcomes.

Renal artery bypass including aortic graft for renovascular hypertension

Abstract Background Renal artery stenosis (RAS) is a rare renal manifestation of tuberous sclerosis (TS). In children, it leads to renovascular hypertension that can be managed medically or surgically. It becomes challenging to treat when other vascular anomalies coexist. Case presentation A 7-year old Caucasian boy with TS presented with hypertension. Renal angiogram showed left RAS and infrarenal abdominal aortic aneurysm (AAA). After percutaneous transluminal angioplasty (PTA) failed to control his renovascular hypertension, we elected to perform renal artery bypass and aortic graft repair of the AAA. In nine years of follow up, he maintained good blood pressure (BP) control with oral antihypertensive medications and required PTA only once for renal artery bypass graft stenosis. Conclusion We present a case of TS associated RAS and AAA treated by renal artery bypass and aortic graft repair with favorable outcome. Our surgical approach may delay progression of renal insufficiency in patients with renovascular hypertension and TS.

Asociación entre hiperkaliemia y evolución clínica en la enfermedad renal crónica avanzada

IntroductionPatients with advanced chronic kidney disease (CKD) are at greatest risk of hyperkalemia (HK). The relationship between HK and negative outcomes (mortality or progression of renal insufficiency) in non-dialysis dependent CKD patients is controversial. AimsTo determine the incidence, prevalence, and factors related with HK in a cohort of CKD patients, and its relationship with mortality, hospitalization rate, CKD progression, and dialysis initiation. Material and methodsA retrospective, observational study in an incident cohort of adult patients with stage 4 or 5 CKD not on dialysis. Inclusion criteria were: having at least three consecutive estimated glomerular filtration rate (eGFR) measurements in a follow-up period >3 months. Decline in renal function was estimated as the slope of the individual linear regression line of eGFR over follow-up time. HK was defined as serum K levels ≥5.5 meq/l. Associations of HK with outcomes were adjusted for major confounding variables in the multivariate analysis. ResultsThe study group consisted of 1079 patients (574 males, mean age: 65±14 years) with mean baseline eGFR 14.8±4.5 ml/min/1,73 m2. Mean follow-up time was 15 months with a median of 7 serum sample determinations per patient. HK was observed at baseline in 26% of patients; in at least one serum sample during the individual follow-up period in 68%; or chronically (>50% of samples) in 33% of patients. By multivariate logistic regression, the best determinants of chronic HK were: male sex (OR = 1.529; 95% CI [1.154-2.025], p = .003), serum bicarbonate (OR = 0.863 [0.829-0.900], p <.0001), diuretic treatment (OR = 0.743 [0.556-0.992], p = .044), and angiotensin converting enzyme inhibitor and/or angiotensin receptor blockers (OR = 4.412 [2.915-6.678], p <.0001). Patients whose serum K levels were in the upper quartile showed a significantly faster CKD progression (−4.05±5.22 vs. −2.69±5.61 ml/min/1.73 m2/year, p <.0001), and more frequent dialysis initiation (63% vs. 57%, p = .115), though lower mortality (9% vs. 17%, p = .003) and hospitalization rates (2.68±5.94 vs. 3.16±6.77 days per year, p = .301) than the other study patients. However, in the multivariate analysis, average serum K levels were not independently associated with the clinical outcomes investigated. ConclusionHK is a common biochemical finding in non-dialysis dependent CKD patients, mainly associated with prescribed medication. However, HK was not independently associated with major negative clinical outcomes.

ACE Inhibitors and ARB in Chronic Kidney Disease: What Has to Be Considered

Proteinuric kidney disease, especially in the early and middle stages of renal insufficiency, may be favorably affected by ACE-I/ARB. The progression of renal insufficiency is thereby slowed down and dialysis obligation occurs later or can even be avoided. This effect is independent of the underlying glomerular kidney disease. In the advanced stage of renal insufficiency, the benefit of ACE-I/ARB cannot yet be conclusively assessed. The interruption of ACE-I/ARB therapy may possibly contribute to a certain recovery of renal function and delay the onset of dialysis a little. However, studies are still pending and the benefits of ACE-I/ARB for the heart and blood vessels, especially at this stage of renal insufficiency, should not be overlooked.Patients with proteinuria benefit from ACE-I/ARB not only in terms of renal stabilization. A cardio-protective effect by reduction of proteinuria and a delay of progression is proven. On the other hand, the protective effect of ACE-I/ARB that can be detected directly on the heart and blood vessels should not be disregarded. Thus, even if chronic renal insufficiency no longer benefits directly from ACE-I/ARB therapy, cardiac protection may still be of great importance to the chronic kidney patient.

Kidney dysfunction in the low-birth weight murine adult: implications of oxidative stress

Maternal undernutrition (MUN) during pregnancy leads to low-birth weight (LBW) neonates that have a reduced kidney nephron endowment and higher morbidity as adults. Using a severe combined caloric and protein-restricted mouse model of MUN to generate LBW mice, we examined the progression of renal insufficiency in LBW adults. Through 6 mo of age, LBW males experienced greater albuminuria (ELISA analysis), a more rapid onset of glomerular hypertrophy, and a worse survival rate than LBW females. In contrast, both sexes experienced a comparable progressive decline in renal vascular density (immunofluorescence analysis), renal blood flow (Laser-Doppler flowmetry analysis), glomerular filtration rate (FITC-sinistrin clearance analysis), and a progressive increase in systemic blood pressure (measured via tail-cuff method). Isolated aortas from both LBW sexes demonstrated reduced vasodilation in response to ACh, indicative of reduced nitric oxide bioavailability and endothelial dysfunction. ELISA and immunofluorescence analysis revealed a significant increase of circulating reactive oxygen species and NADPH oxidase type 4 (NOX4) expression in both LBW sexes, although these increases were more pronounced in males. Although more effective in males, chronic tempol treatment did improve all observed pathologies in both sexes of LBW mice. Chronic NOX4 inhibition with GKT137831 was more effective than tempol in preventing pathologies in LBW males. In conclusion, despite some minor differences, LBW female and male adults have a reduced nephron endowment comparable with progressive renal and vascular dysfunction, which is associated with increased oxidative stress and subsequent endothelial dysfunction. Tempol treatment and/or NOX4 inhibition attenuates renal and vascular dysfunction in LBW adults.

Role of Kidney Biopsies for Biomarker Discovery in Diabetic Kidney Disease.

Although estimated glomerular filtration rate and albuminuria are well-established biomarkers of diabetic kidney disease (DKD), additional biomarkers are needed, especially for the early stages of the disease when both albuminuria and estimated glomerular filtration rate may still be in the normal range and are less helpful for identifying those at risk of progression. Traditional biomarker studies for early DKD are challenging because of a lack of good early clinical end points, and most rely on changes in existing imprecise biomarkers to assess the value of new biomarkers. There are well-characterized changes in kidney structure, however, that are highly correlated with kidney function, always precede the clinical findings of DKD and, at preclinical stages, predict DKD progression. These structural parameters may thus serve as clinically useful end points for identifying new biomarkers of early DKD. In addition, investigators are analyzing tissue transcriptomic data to identify pathways involved in early DKD which may have associated candidate biomarkers measurable in blood or urine, and differentially expressed microRNAs and epigenetic modifications in kidney tissue are beginning to yield important observations which may be useful in identifying new clinically useful biomarkers. This review examines the emerging literature on the use of kidney tissue in biomarker discovery in DKD.

La charge acide d’origine alimentaire : une nouvelle cible pour le néphrologue ?

The acid production of endogenous origin depends mainly on the metabolism of the food and varies with the nature of these. Of the order of 1mEq/kg/day for contemporary food in industrialized countries, it is reduced by more than one third among vegetarians and close to neutrality among vegans. The dietary acid load is eliminated by the normal kidneys, thus maintaining the acid-base equilibrium. In the setting of CKD, it will overflow the capacities of the nephrons, generating a retention of H+ ions, promoting subclinical acidosis. This tissue retention of H+ ions was confirmed by direct techniques in animal models and indirect techniques in humans. The systemic retention of H+ ions and the accompanying compensatory mechanisms have negative consequences on bone tissue, skeletal muscle, cardiovascular risk and renal function. In the animal, the substitution of casein (acid) by soy (alkaline) prevents metabolic acidosis and slows the progression of renal insufficiency. In man, various prospective studies have confirmed that the risk of renal insufficiency was positively correlated with the dietary acid load. Conversely, bicarbonate supplementation and/or a diet enriched with fruits and vegetables, have a favorable effect on renal insufficiency, including in subjects with normal bicarbonate. These results lead to reconsider the K/DOQI recommendations to correct acidosis when the bicarbonate level falls below 22mEq/L, since tissue retention of H+ ions and its negative consequences appear at higher or even normal levels of bicarbonates.

Progression of Renal Insufficiency in Patients with Essential Hypertension Treated with Renin Angiotensin Aldosterone System Blockers: An Electrocardiographic Correlation.

Background: There is a frequent association between renal insufficiency and cardiovascular disease in patients with essential hypertension (HTN). The aim of this study was to analyze the relationship between ECG parameters and the progress of renal damage in patients with treated HTN. Methods: 109 patients with HTN had their microalbuminuria monitored over a 3-year time frame. During the last 3 months of follow-up, an ECG was recorded. Patients were divided into 3 groups according to the deterioration of their renal function: normoalbuminuria during the study period (normo–normo; n = 51); normoalbuminuria developing microalbuminuria (normo–micro; n = 29); and microalbuminuria at baseline (micro–micro; n = 29). Results: There were no differences in presence of left ventricular hypertrophy between the 3 groups. RV6/RV5 >1 was observed more frequently as renal function declined (p = 0.025). The 12-lead QRS-complex voltage-duration product was significantly increased in patients without microalbuminuria at baseline who went on to develop microalbuminuria (p = 0.006). Patients who developed microalbuminuria during follow-up, with positive Cornell voltage criteria, showed a lesser degree of progression of microalbuminuria when compared with the rest of the subgroups (p = 0.044). Furthermore, patients with microalbuminuria at baseline treated with angiotensin receptor blockers and diuretics, and positive Cornell voltage criteria, showed a higher degree of microalbuminuria compared to those with negative Cornell voltage criteria (p = 0.016). Conclusions: In patients with HTN, we identified some ECG parameters, which predict renal disease progression in patients with HTN, which may permit the identification of patients who are at risk of renal disease progression, despite optimal antihypertensive pharmacotherapy.