Manifestation Of Chronic Kidney Disease Research Articles

English

A 55-year-old man presented with decreased urine output and altered sensorium of a week’s duration. On examination, asterixis was present. Examination of his hands revealed pinkish bands on the distal part of his nails with whitened proximal nails. Further evaluation revealed deranged kidney function tests (blood urea,189 mg/dL and serum creatinine, 8.8 mg/dL) and bilaterally shrunken kidneys. A diagnosis of chronic kidney failure with renal encephalopathy was established and the patient initiated on haemodialysis, and later he was discharged. First described by Lindsay,1 half-and-half nails are a specific manifestation of chronic kidney disease (CKD). It is seen in about 28% of patients with CKD.2 The pathogenesis of this manifestation is not known. Although it is reported to disappear with kidney transplantation within few weeks, dialysis has no effects on it. Half-and-half nails have no relation with severity of CKD. The presence of these nail changes warrant evaluation to rule out azotemia.3

Compromised calcium and phosphorus metabolism in patients with diabetes mellitus and chronic kidney disease

Disturbance of bone and mineral metabolism (BMM) is one of manifestations of chronic kidney disease (CKD), but its significance goes beyond bone disorders per se. Current discourse is as broad as to include vascular calcification, anemia and arterial hypertension, - conditions increasing mortality in patients with CKD. In this regard the active search for and development of novel approach to correction of BMM is under way. Apart from capacity to normalize calcium and phosphorus metabolism, parathyroid hormone secretion and to reduce morphologic alterations of bone tissue, modern therapeutic agents feature cardio- and renoprotective capabilities, which make them a treatment of choice for compromised BMM in CKD.

Ocular manifestations of chronic kidney disease among adult patients receiving hemodialysis

The loss of an organ is a devastating event. The potential of visual loss is a reality a patient with chronic kidney disease has to live with. It is interesting to note that many patients are weighed down by their present diagnosis, and resources, financial and otherwise are directed toward this condition to the exclusion of others. A patient may therefore not notice or complain of visual symptoms until vision is irreversibly lost. At another end of the spectrum is an undiagnosed case of chronic kidney disease, with its ocular manifestations, presenting first to an ophthalmologist. Visual loss can occur from the primary cause of the disease, renal insufficiency and its complications and renal replacement therapy (hemodialysis or renal transplant). The focus in the management of chronic kidney disease has shifted from treatment-only to prevention and delay of progression, with a view of increasing life expectancy and quality of life. This should also include ocular health as the onset and progression of potentially vision-threatening conditions can have great implications in the everyday life of a patient with chronic kidney disease. This special report aims to highlight the importance of ocular examination in this group of patients so that necessary counseling can be given and treatment instituted, when indicated, before irreversible visual impairment occurs.

Preoperative masked renal damage in Japanese patients with primary aldosteronism: Identification of predictors for chronic kidney disease manifested after adrenalectomy

Correct interpretation of renal function in patients with primary aldosteronism is difficult before adrenalectomy, because subtle kidney impairment is often masked by glomerular hyperfiltration peculiar to primary aldosteronism. The aim of this study was to investigate postoperative changes in renal function for patients with primary aldosteronism and to identify clinical predictors of chronic kidney disease manifested postoperatively in the patients without pre-existing chronic kidney disease. Records of 78 Japanese patients who underwent unilateral adrenalectomy for primary aldosteronism were retrospectively surveyed. Patients who had been followed up for <6 months were excluded. Preoperative and postoperative estimated glomerular filtration rate were compared. Furthermore, uni- and multivariate analyses were carried out to identify clinical predictors for chronic kidney disease manifested postoperatively. Patients with preoperative estimated glomerular filtration rate ≥60 mL/min/1.73 m(2) showed a significant decrease after surgery. Of the 66 patients without pre-existing chronic kidney disease, 24 developed chronic kidney disease postoperatively. Multivariate logistic regression analysis identified a medical history of dyslipidemia as an independent predictor for chronic kidney disease manifested postoperatively. According to univariate analyses, additional factors associated with postoperative manifestation of chronic kidney disease included older age, lower diastolic blood pressure and lower estimated glomerular filtration rate. The interpretation of normal or abnormal renal functions by examining estimated glomerular filtration rate heightened by hyperfiltration alone can mislead clinicians before adrenalectomy. Clinicians should pay attention to patients at greater risk of a significant decline in postoperative renal function.

Fanconi syndrome and chronic kidney disease in paroxysmal nocturnal hemoglobinuria: effect of eculizumab therapy

The association of Fanconi syndrome (FS) and chronic kidney disease (CKD) has been rarely described during the course of paroxysmal nocturnal hemoglobinuria (PNH). We report 2 patients with PNH and CKD associated with proximal tubule dysfunction, which manifested as full-blown FS in one case. In both patients, abnormal iron load within the kidneys was demonstrated by magnetic resonance imaging, which correlated with diffuse and numerous hemosiderin inclusions within proximal tubular cells. After 12 months, eculizumab treatment resulted in significant decrease in the kidney iron load in both cases. Glomerular filtration rate improved in one case and was stabilized in the other, in whom pretreatment kidney biopsy had shown severe extensive interstitial fibrosis. However, symptoms of proximal tubular dysfunction persisted in both patients. These data suggest that hemosiderin deposition in proximal tubules is probably an important mechanism involved in the development of FS, an under recognized and early manifestation of CKD in PNH. Prolonged treatment with eculizumab may improve long-term renal function in PNH patients with CKD.

Validated SNPs for eGFR and their associations with albuminuria

Albuminuria and reduced glomerular filtration rate are manifestations of chronic kidney disease (CKD) that predict end-stage renal disease, acute kidney injury, cardiovascular disease and death. We hypothesized that SNPs identified in association with the estimated glomerular filtration rate (eGFR) would also be associated with albuminuria. Within the CKDGen Consortium cohort (n= 31 580, European ancestry), we tested 16 eGFR-associated SNPs for association with the urinary albumin-to-creatinine ratio (UACR) and albuminuria [UACR >25 mg/g (women); 17 mg/g (men)]. In parallel, within the CARe Renal Consortium (n= 5569, African ancestry), we tested seven eGFR-associated SNPs for association with the UACR. We used a Bonferroni-corrected P-value of 0.003 (0.05/16) in CKDGen and 0.007 (0.05/7) in CARe. We also assessed whether the 16 eGFR SNPs were associated with the UACR in aggregate using a beta-weighted genotype score. In the CKDGen Consortium, the minor A allele of rs17319721 in the SHROOM3 gene, known to be associated with a lower eGFR, was associated with lower ln(UACR) levels (beta = -0.034, P-value = 0.0002). No additional eGFR-associated SNPs met the Bonferroni-corrected P-value threshold of 0.003 for either UACR or albuminuria. In the CARe Renal Consortium, there were no associations between SNPs and UACR with a P< 0.007. Although we found the genotype score to be associated with albuminuria (P= 0.0006), this result was driven almost entirely by the known SHROOM3 variant, rs17319721. Removal of rs17319721 resulted in a P-value 0.03, indicating a weak residual aggregate signal. No alleles, previously demonstrated to be associated with a lower eGFR, were associated with the UACR or albuminuria, suggesting that there may be distinct genetic components for these traits.

Posterior reversible encephalopathy syndrome as the first manifestation of chronic kidney disease

Posterior reversible encephalopathy syndrome (PRES), a term coined in 1996, describes a clinico-radiologic entity characterised by headache, seizures, decreased vision, impaired consciousness and white matter oedema in bilateral occipito-parietal regions [1]. Hypertensive encephalopathy, eclampsia, immunosuppressive/cytotoxic drugs, organ transplantation, renal disease, autoimmune diseases and vasculitides are reported risk factors of PRES [1, 2]. Although potentially reversible, delay in treatment can result in permanent brain damage [3, 4].

Distinct effects on long-term function of injured and contralateral kidneys following unilateral renal ischemia-reperfusion

Salt-sensitive hypertension and chronic kidney disease (CKD) following recovery from acute kidney injury (AKI) may occur secondary to incomplete repair, or by activation of circulating factors stimulated by injury. We created two types of renal injury induced by unilateral ischemia-reperfusion (I/R); in a direct/ipsilateral AKI group, rats were subjected to unilateral I/R and the untouched contralateral kidney was removed by unilateral nephrectomy after 5 wk to isolate effects on the injured kidney. In the remote/contralateral AKI group, the injured kidney was removed after 5 wk to isolate effects on the untouched kidney. When these animals were subsequently challenged with elevated dietary sodium for an additional 4 wk (0.4 to 4%), both remote/contralateral and direct/ipsilateral AKI rats manifested a significant increase in blood pressure relative to sham-operated controls. Similarly, in acute studies, both ipsilateral and contralateral kidneys had impaired pressure natriuresis and hemodynamic responses. Reductions in vascular density were observed following direct/ipsilateral injury, but were not observed in the remote/contralateral kidney. However, both remote/contralateral and direct/ipsilateral kidneys contained interstitial cells, some of which were identified as activated (low CD62L/CD4+) T lymphocytes. In contrast, only the direct/ipsilateral AKI group demonstrated significant CKD following exposure to elevated salt. This was characterized by a significant reduction in creatinine clearance, an increase in albuminuria, and a dramatic expansion of interstitial inflammation. Taken together, these data suggest that the salt-sensitive features of AKI on hypertension and CKD are segregable such that effects on hemodynamics and hypertension occur independent of direct renal damage. However, prior direct injury to the kidney is required to elicit the full manifestation of CKD induced by elevated sodium intake.

Optimal frequency of parathyroid hormone monitoring in chronic hemodialysis patients

Secondary hyperparathyroidism is a common manifestation of chronic kidney disease (CKD). Serum parathyroid hormone (PTH) level is widely used as a marker for hyperparathyroidism. Currently, there is limited data to guide the frequency of PTH monitoring in CKD patients. The present study was undertaken to determine the optimal frequency of monitoring PTH in patients on maintenance hemodialysis. A cohort of 154 patients on maintenance dialysis at a single outpatient hemodialysis center was included in this retrospective study. In Phase I of the study, PTH was measured every 3 months as per Kidney Disease Outcomes Quality Initiative (KDOQI) recommendations. In Phase II, PTH was measured monthly. In both phases, dietary education and optimization of medications including phosphate binders, vitamin D analogues and calcimimetics were implemented using standard protocols Data from the two phases was compared with each other and with their respective national norms. The percentage of patients with PTH in target range of 150 - 300 pg/ml increased significantly from Phase I to Phase II of the study (25.4 - 40.3%, p < 0.01). There was a significant reduction in the percentage of patients with PTH levels > 300 pg/ml in Phase II compared with national averages (37% vs. 47%, p < 0.02). There was no significant difference in calcium and phosphorus levels or their product. There was a significant increase in the usage of calcimimetics and vitamin D analogues. We observed that increasing the frequency of monitoring PTH from quarterly to monthly was associated with a significant increase in the percentage of patients reaching KDOQI target PTH values.

Lack of modulatory effect of simvastatin on indoxyl sulfate-induced activation of cultured endothelial cells

Aims Endothelial dysfunction is a common manifestation of chronic kidney disease (CKD). The protein-bound uremic toxins have emerged as important factors associated with cardiovascular disease and the outcome of CKD. The effect of indoxyl sulfate (IS) on endothelial cells remains unclear. Main methods Human umbilical endothelial cells (HUVEC) were incubated using IS at two concentrations: 100 μM and 1000 μM over two periods of time: 16 and 48 h. HUVEC were also pre-treated with simvastatin to examine its effect. RT-PCR was used to assess changes in the gene expression of intracellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), Monocyte chemotactic protein-1 (MCP-1), E-selectin, and angiotensin receptor type 1 (AT1R). Protein abundance of the investigated molecules was assessed by immunoblotting. Key findings Treatment with 100 μM IS for 16 h induced a 2-fold increase in the expression of ICAM-1, VCAM-1, and MCP-1. At a concentration of 1000 μM, there was a 2–3-fold increase. An extended treatment period at low concentrations was associated with a 2–3 fold increase and the increase of ICAM-1 and VCAM-1 was more prominent under high concentration. Results of immunoblotting confirmed an increase in the abundance of ICAM-1, VCAM-1 and MCP-1. No significant change was noted in E-selectin and AT1R according to concentration or treatment duration. Pre-treatment with simvastatin did not alter IS-induced changes. Significance IS increased the expression of adhesion molecules of endothelial cells exhibiting a concentration and duration dependent pattern. Simvastatin did not demonstrate any effect on IS-associated endothelial activation.

Association of Sleep-Related Problems With CKD in the United States, 2005-2008

Sleep-related problems, which have been associated with poor health outcomes, have not been investigated thoroughly in people with chronic kidney disease (CKD). We examined the prevalence of a variety of sleep-related problems in persons with and without CKD. National cross-sectional survey (National Health and Nutrition Examination Survey 2005-2008). Community-based survey of 9,110 noninstitutionalized US civilian residents 20 years or older. CKD, defined as estimated glomerular filtration rate (eGFR) of 15-59 mL/min/1.73 m(2) (stages 3 and 4) or eGFR ≥60 mL/min/1.73 m(2) and albumin-creatinine ratio ≥30 mg/g (stages 1 and 2). Sleep quality, defined using self-report in a multi-item sleep questionnaire including items from previously validated instruments. Albuminuria and eGFR assessed from urine and blood samples; sleep, demographics, and comorbid conditions assessed using a standardized questionnaire. Inadequate sleep (≤6 hours per night) differed by CKD severity (37.4%, 43.0%, and 30.9% for no CKD, CKD stages 1 and 2, and CKD stages 3 and 4, respectively; P = 0.003). Frequent sleeping pill use (8.4%, 9.9%, and 16.6%), leg symptoms (39.2%, 48.0%, and 50.9%), and nocturia (20.9%, 35.2%, and 43.6%; P < 0.001 for all) also differed by CKD severity. After adjustment for age, sex, race/ethnicity, obesity, diabetes, and cardiovascular disease, the prevalence of these sleep-related problems remained higher in people with CKD stages 1 and 2 relative to no CKD. Most other measures of sleep quality, disorder, and functional outcomes did not differ by CKD. Inability to establish causality and possible unmeasured confounding. Providers should be aware of early sleep-related CKD manifestations, including inadequate sleep, leg symptoms, and nocturia, and of the high rate of reported sleep medication use in this population.

Fibroblast growth factor 23 is elevated before parathyroid hormone and phosphate in chronic kidney disease

Fibroblast growth factor 23 (FGF23) regulates phosphorus metabolism and is a strong predictor of mortality in dialysis patients. FGF23 is thought to be an early biomarker of disordered phosphorus metabolism in the initial stages of chronic kidney disease (CKD). We measured FGF23 in baseline samples from 3879 patients in the Chronic Renal Insufficiency Cohort study, which is a diverse cohort of patients with CKD stage 2-4. Mean serum phosphate and median parathyroid hormone (PTH) levels were in the normal range, but median FGF23 was markedly greater than in healthy populations, and increased significantly with decreasing estimated glomerular filtration rate (eGFR). High levels of FGF23, defined as being above 100 RU/ml, were more common than secondary hyperparathyroidism and hyperphosphatemia in all strata of eGFR. The threshold of eGFR at which the slope of FGF23 increased was significantly higher than the corresponding threshold for PTH based on non-overlapping 95% confidence intervals. Thus, increased FGF23 is a common manifestation of CKD that develops earlier than increased phosphate or PTH. Hence, FGF23 measurements may be a sensitive early biomarker of disordered phosphorus metabolism in patients with CKD and normal serum phosphate levels.

Bilateral quadriceps tendon rupture as the presenting manifestation of chronic kidney disease

Bilateral painful knees with loss of extension in a patient with chronic kidney disease (CKD) may be due to spontaneous quadriceps tendon rupture. This rare complication is usually seen in patients on long term dialysis. We present a case of bilateral spontaneous quadriceps tendon rupture demonstrated by magnetic resonance imaging in a 20-year-old woman who on evaluation was found to have CKD.

Silent cerebral infarction is associated with the development and progression of nephropathy in patients with type 2 diabetes

Chronic kidney disease (CKD) is an important risk factor for cardiovascular disease in patients with diabetes. The relationship between renal manifestations of CKD (albuminuria and decreased glomerular filtration rate) and silent cerebral infarction (SCI) has attracted attention; however, most studies examined the effects of components of CKD on prevalence of SCI. We sought to assess the relationship between SCI and the development and progression of nephropathy in type 2 diabetic patients. We studied 366 type 2 diabetic patients with normoalbuminuria (urinary albumin-to-creatinine ratio [ACR] <30 mg g(-1), N=246) or microalbuminuria (ACR=30-299 mg g(-1), N=120). SCI was defined by cranial MRI. The primary end point was progression from normo- to microalbuminuria or from micro- to macroalbuminuria. The cumulative incidence of the primary end point was estimated using the Kaplan-Meier method. Risk estimates for reaching the end point were calculated using Cox proportional hazard model analyses. During a median follow-up period of 3.9 years, 23 normoalbuminuric and 24 microalbuminuric patients reached the primary end point. Patients with SCI (N=171) had a greater incidence of reaching the end point than those without SCI (N=195, P=0.020 by the log-rank test), with a hazard ratio of 2.02 (95% confidence interval=1.09-3.72, P=0.025) in the multivariate Cox regression model. Although the common pathogenesis of SCI and albuminuria in diabetic patients is still unclear, SCI may be a predictor of progression of nephropathy in type 2 diabetic patients.

NMR identifies atherogenic lipoprotein abnormalities in early diabetic nephropathy that are unrecognized by conventional analysis

Lipoprotein abnormalities are likely contributors to the high risk of cardiovascular disease in the chronic kidney disease (CKD) population, although information is limited. Specifically, little is known about lipoprotein abnormalities during the early stages of diabetic kidney disease. The aim of this study was to investigate the relationship between lipoproteins and early manifestations of CKD in the 517 Type 2 diabetes mellitus (T2DM) patients who participated in the Insulin Resistance Atherosclerosis Study (IRAS). Lipoprotein abnormalities were measured by conventional lipid analysis, nuclear magnetic resonance (NMR) spectroscopy, gel gradient electrophoresis (GE), immunoprecipitation (IP), and ELISA. We grouped the cases into albumin to creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) quartiles. In the conventional lipid analysis, triglycerides (TG) correlated directly with ACR and inversely with eGFR quartiles (p = 0.01), while LDL, HDL cholesterol did not correlate with change in ACR or eGFR. ACR was directly associated with apoB, total VLDL, medium VLDL, IDL and small LDL particle concentrations (p < or = 0.03), and inversely with large LDL particles (p = 0.01) and LDL size (p = 0.008). Estimated GFR quartiles were inversely associated with total VLDL, small VLDL, IDL, and medium HDL particles (p < or = 0.01). In subjects with T2DM, mild albuminuria and reduction in eGFR were associated with numerous atherogenic lipoprotein abnormalities that were detected by the combination of NMR spectroscopy, gel gradient electrophoresis, immunoprecipitation and ELISA but not by the standard clinical lipid analysis.

A Prospective Study of Albuminuria and Cognitive Function in Older Adults: The Rancho Bernardo Study

Chronic kidney disease is a risk factor for cognitive impairment. Albuminuria is an early manifestation of chronic kidney disease and a marker of endothelial dysfunction and vascular risk. Results of prior studies of albuminuria and cognitive function are contradictory. The authors studied 1,345 community-dwelling women and men in southern California (mean age, 75 years) at a 1992-1996 research clinic visit, when urine albumin/creatinine ratio (ACR) was measured in spot morning urine and cognitive function was evaluated by using the Mini-Mental State Examination Trail-Making Test B, and category fluency test. An ACR of > or =30 mg/g was found in 17% of women and 15% of men in 1992-1996. Analysis of covariance was used to compare cognitive function score by categorical ACR. Between 1999 and 2002, 759 participants returned for repeat cognitive function testing. For men, but not women, baseline albuminuria, but not estimated glomerular filtration rate, was associated with reduced cognitive function at follow-up on all tests (P's < 0.05). An ACR of > or =30 mg/g was associated with greater annual decline in Mini-Mental State Examination and category fluency scores. Albuminuria may be an easily measured marker predicting future cognitive function decline. Results imply a common underlying mechanism affecting the renal and cerebral microvasculature.

Renal fibrosis

Renal fibrosis, characterized by tubulointerstitial fibrosis and glomerulosclerosis, is the final manifestation of chronic kidney disease. Renal fibrosis is characterized by an excessive accumulation and deposition of extracellular matrix components. This pathologic result usually originates from both underlying complicated cellular activities such as epithelial-to-mesenchymal transition, fibroblast activation, monocyte/macrophage infiltration, and cellular apoptosis and the activation of signaling molecules such as transforming growth factor beta and angiotensin II. However, because the pathogenesis of renal fibrosis is extremely complicated and our knowledge regarding this condition is still limited, further studies are needed.

Managing the anaemia of chronic kidney disease

Summary Anaemia is a common manifestation of chronic kidney disease, especially when the glomerular filtration rate falls below 30 m l/min. It is important to exclude other causes of anaemia such as iron and other haematinic deficiencies, chronic inflammation, malignancy and drugs. After reversible causes of anaemia are excluded, supplementary erythropoietin (epoetin) can be considered when the patient's haemoglobin concentration falls below 100 g/ l. Patients treated with epoetin often require supplements of oral or intravenous iron to maintain adequate iron stores during the correction and the maintenance phases of management. The main adverse effect of epoetin use is the development or worsening of hypertension. Care must also be taken not to overshoot the target haemoglobin of 110–120 g/ l, as this can be associated with a prothrombotic tendency.

Acidose metabólica na doença renal crônica: abordagem nutricional

A acidose metabólica é uma das complicações da doença renal crônica e está associada ao aumento do catabolismo protéico, à diminuição da síntese de proteínas e ao balanço nitrogenado negativo. A dieta tem forte influência sobre a geração de ácidos, podendo contribuir, portanto, para determinar a gravidade da acidose no paciente com doença renal crônica. Alguns pesquisadores têm observado que é possível estimar a excreção ácida renal, e que o cálculo dessa carga ácida a partir de alguns componentes da dieta, permitiria uma predição apropriada dos efeitos da dieta na acidose metabólica. Este artigo é uma comunicação sobre as bases fisiológicas, bem como as implicações clínicas da acidose em pacientes com doença renal crônica e a influência da dieta no balanço ácido-básico desses pacientes.

Anemia in chronic kidney disease: causes, diagnosis, treatment.

Most patients with chronic kidney disease eventually become anemic. We should view the management of anemia in these patients as part of the overall management of the many clinically relevant manifestations of chronic kidney disease. Erythropoiesis-stimulating agents (ESAs) are safe and should be used, as treating anemia may forestall some of the target-organ damage of chronic kidney disease.