The Clinical Course of Minimal Change Nephrotic Syndrome With Onset in Adulthood or Late Adolescence: A Case Series.

BACKGROUND: Few studies have examined the treatment and outcome of adult-onset minimal change nephrotic syndrome (MCNS). We retrospectively studied 125 patients who had MCNS with onset in either adulthood or late adolescence. Presenting characteristics, duration of initial treatment and response to treatment, relapse patterns, complications, and long-term outcome were studied. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: Patients with new-onset nephrotic syndrome 16 years or older and a histologic diagnosis of MCNS in 1985 to 2011 were identified from pathology records of 10 participating centers. OUTCOMES: Partial and complete remission, treatment resistance, relapse, complications, renal survival. RESULTS: Corticosteroids were given as initial treatment in 105 (84%) patients. After 16 weeks of corticosteroid treatment, 92 (88%) of these patients had reached remission. Median time to remission was 4 (IQR, 2-7) weeks. 7 (6%) patients initially received cyclophosphamide with or without corticosteroids, and all attained remission after a median of 4 (IQR, 3-11) weeks. 13 (10%) patients reached remission without immunosuppressive treatment. One or more relapses were observed in 57 (54%) patients who received initial corticosteroid treatment. Second-line cyclophosphamide resulted in stable remission in 57% of patients with relapsing MCNS. Acute kidney injury was observed in 50 (40%) patients. Recovery of kidney function occurred almost without exception. Arterial or venous thrombosis occurred in 11 (9%) patients. At the last follow-up, 113 (90%) patients were in remission and had preserved kidney function. 3 patients with steroid-resistant MCNS progressed to end-stage renal disease, which was associated with focal segmental glomerulosclerosis lesions on repeat biopsy. LIMITATIONS: Retrospective design, variable treatment protocols. CONCLUSIONS: The large majority of patients who had MCNS with onset in adulthood or late adolescence were treated with corticosteroids and reached remission, but many had relapses. Cyclophosphamide resulted in stable remission in many patients with relapses. Significant morbidity was observed due to acute kidney injury and other complications. Progression to end-stage renal disease occurred in a few patients and was explained by focal segmental glomerulosclerosis.

Episodic electrolyte disorders and renal failure due to a rare disease: the McKittrick-Wheelock syndrome.

We describe a patient with intermittent bouts of malaise and muscle weakness due to profound electrolyte disturbances. Colonoscopy showed a giant villous adenoma of the sigmoid. The patient was diagnosed with a McKittrick-Wheelock syndrome with pre-renal disease and electrolyte disorders due to periodic rectal fluid loss. The diagnosis was delayed by the patient's misinterpretation of the doctor's questions. In cases where the patient's history is contrary to what the data reveal, the expected culprit organ should be investigated early in the course of the disease. Extracting relevant and guiding information out of the patient's history remains an important skill.

Prognostic value of aortic stiffness and calcification for cardiovascular events and mortality in dialysis patients: outcome of the calcification outcome in renal disease (CORD) study.

BACKGROUND AND OBJECTIVES: Radiographic calcification and arterial stiffness each individually are predictive of outcome in dialysis patients. However, it is unknown whether combined assessment of these intermediate endpoints also provides additional predictive value. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Scoring of abdominal aortic calcification (AAC) using plain lateral abdominal x-ray and measurement of carotid-femoral pulse wave velocity (PWV) were performed in a cohort of 1084 prevalent dialysis patients recruited from 47 European dialysis centers. RESULTS: During a follow-up of 2 years, 234 deaths and 91 nonfatal cardiovascular (CV) events occurred. Compared with the lowest tertile of AAC, the risk of an event was increased by a factor 3.7 in patients with a score of 5 to 15 (middle tertile), and by a factor 8.6 in patients with scores of 16 to 24. Additionally, each 1-m/s increase in PWV was associated with a 15% higher risk. At higher AAC (scores ≥ 5), the effect of PWV was attenuated because of a negative PWV × AAC interaction (hazard ratio [HR]: 0.895 and 0.865 for middle and upper AAC tertiles). After accounting for age, diabetes, and serum albumin, AAC and PWV remained independent predictors of outcome. CONCLUSIONS: AAC and central arterial stiffness are independent predictors of mortality and nonfatal CV events in dialysis patients. The risk associated with an increased PWV is less pronounced at higher levels of calcification. Assessment of AAC and PWV is feasible in a clinical setting and both may be used for an accurate CV risk estimation in this heterogeneous population.

Abdominal aortic calcification in dialysis patients: results of the CORD study.

BACKGROUND: Patients with chronic kidney disease stage 5 have a high prevalence of vascular calcification, but the specific anatomical distribution and severity of abdominal aortic calcification (AAC), in contrast to coronary calcification, is less well documented. AAC may be recorded using plain radiographs. The present report is an analysis of baseline data on AAC in patients enrolled in the CORD (Calcification Outcome in Renal Disease) study. METHODS: A total of 47 centres in six European countries participated in this cross-sectional study. Inclusion criteria were age >or=18 years and duration of dialysis >or=3 months. Lateral lumbar radiography of the abdominal aorta was used to determine the overall AAC score, which is related to the severity of calcific deposits at lumbar vertebral segments L1-L4. The reliability of the method was tested by double reading of 64 radiographs (coefficient of correlation 0.9). RESULTS: A lateral lumbar radiograph was obtained in 933 patients. Calcification (AAC score >or= 1) was present in 81% of the patients; its severity increased significantly from L1 to L4 (P < 0.0001) and affected all of these segments in 51% of patients. Independent predictors for the presence and severity of calcification were age (odds ratio [OR] 1.103/year; P < 0.0001), duration of dialysis (OR 1.110/year; P = 0.002) and history of cardiovascular disease (OR 3.247; P < 0.0001). CONCLUSIONS: AAC detected by lateral lumbar radiograph is associated with several risk factors of uraemic calcification. This semi-quantitative method is more widely available and less expensive than the current procedures for studying calcification and could form part of a pre-transplant workup and cardiovascular risk stratification.

Undercarboxylated matrix GLA protein levels are decreased in dialysis patients and related to parameters of calcium-phosphate metabolism and aortic augmentation index.

BACKGROUND: Vascular calcifications are related to cardiovascular mortality and morbidity in dialysis patients. Limited data exist on the role of calcification inhibitors, such as matrix-carboxyglutamic acid protein (MGP) in dialysis patients. METHODS: In 120 dialysis patients and 41 age-matched healthy controls, circulating undercarboxylated (uc) MGP levels were measured with a novel ELISA-based competitive assay. The association between ucMGP levels and determinants of bone mineral metabolism, including the calcification inhibitor fetuin-A, was studied. Moreover, the relation between ucMGP levels and arterial stiffness was investigated. RESULTS: The ucMGP level was significantly lower in dialysis patients compared to controls (173 +/- 70 vs. 424 +/- 126 nmol/l; p < 0.0001). After adjustment for age, sex and duration of dialysis an independent negative association between time-averaged phosphate levels [regression coefficient beta with 95% confidence interval = -64 (-107 to -21)] and a positive association between serum ucMGP and fetuin-A [131 (55-208)] was observed. Duration of dialysis was inversely correlated with ucMGP (r = -0.24, p = 0.007). ucMGP levels were not related to high-sensitivity C-reactive protein or time-averaged calcium levels. After adjustment for age, sex, cardiovascular disease, diabetes, height and mean arterial pressure, ucMGP level was negatively associated with the aortic augmentation index [-0.036 (-0.061 to -0.010)] but not with pulse wave velocity or pulse pressure. CONCLUSION: Significantly lower serum ucMGP levels were observed in dialysis patients compared to healthy controls. ucMGP levels were inversely associated with phosphate and positively associated with serum fetuin-A levels. Furthermore, ucMGP levels were inversely associated with the aortic augmentation index. These data suggest that low ucMGP levels may be a marker of active calcification.

Spatial inhomogeneity of common carotid artery intima-media is increased in dialysis patients.

BACKGROUND: Structural abnormalities of the common carotid artery (CCA), as assessed by ultrasound techniques, are related to cardiovascular outcome in dialysis patients. An increased intima media thickness (IMT) of the CCA may both represent a reaction to a haemodynamic burden as well as atherosclerosis. With a new ultrasound technique CCA-IMT and IMT-inhomogeneity, a novel parameter of spatial variance of the IMT, were measured and related to traditional and non-traditional risk factors. METHODS: In a cross-sectional study, we included 134 dialysis patients, aged 61+/-13 years (103 on haemodialysis, 31 on peritoneal dialysis) and 41 controls, aged 60+/-8 years. Age, sex, pulse pressure, diabetes, prevalent cardiovascular disease (CVD) and height were included in the basic multiregression analysis. Ultrasound examination of the CCA was performed. We also measured serum fetuin-A, high-sensitivity C-reactive protein (hsCRP), antibodies to oxidized low density lipoproteins (anti-oxLDL antibodies), calcium, phosphate, albumin and parathyroid hormone. RESULTS: Compared with controls, dialysis patients had a greater CCA-IMT (670 microm vs 590+/-10 microm; P=0.002) and a greater CCA-IMT inhomogeneity (11.0 vs 8.1%; P=0.013). Dialysis patients with CVD had a greater CCA-IMT (734 microm vs 631 microm; P=0.001) and IMT-inhomogeneity (13.2 vs 9.7; P=0.008) compared with patients without CVD. IMT-inhomogeneity strongly correlated with IMT (R=0.65, P<0.0001). In multiregression analysis, serum fetuin-A and anti-oxLDL antibodies correlated with IMT-inhomogeneity but not with IMT. HsCRP neither correlated with IMT-inhomogeneity nor with IMT. CONCLUSION: The present study shows that CCA-IMT and IMT-inhomogeneity were increased in dialysis patients compared with controls. Although CCA-IMT and IMT-inhomogeneity are related, the different associations between both measurements and non-traditional risk factors show that they are distinct entities.

Study on the relationship of serum fetuin-A concentration with aortic stiffness in patients on dialysis.

BACKGROUND: An increase in aortic stiffness, as reflected by an increase in pulse wave velocity (PWV) or aortic augmentation index (AI) is an important predictor of cardiovascular mortality in dialysis patients. Dysregulation of calcification inhibitors, such as fetuin-A, is involved in vascular pathology in dialysis patients and fetuin-A is inversely related to mortality in dialysis patients. In this study, the relation between serum fetuin-A concentration and parameters of aortic stiffness was investigated in patients with end-stage renal disease. METHODS: In a cross-sectional study we included 131 dialysis patients, aged 62+/-14 years (33 on peritoneal dialysis and 98 on haemodialysis), and 41 controls, aged 60+/-8 years. Time-averaged pre-dialysis values of serum albumin, Ca, P and intact parathyroid hormone were included in multiregression analysis, as were high-sensitivity C-reactive protein (hsCRP), fetuin-A, age, mean arterial pressure (MAP) and dialysis modality. PWV and AI were measured with the SphygmoCor device. RESULTS: Mean fetuin-A concentration in dialysis patients (0.63+/-0.16 g/l) did not differ from controls (0.63+/-0.11 g/l). Median hsCRP levels in dialysis patients were higher compared with controls (4.0 vs 1.9 mg/l; P<0.0001). PWV but not AI was higher in dialysis patients than in controls (9.9 vs 7.9 m/s; P<0.0001). In univariate analysis in dialysis patients, fetuin-A levels were inversely related to both PWV (r = - 0.25, P = 0.007) and AI (r = - 0.26, P = 0.006), respectively. However, after correction for age, gender, MAP and diabetes mellitus, this relation lost statistical significance. CONCLUSIONS: In a dialysis population with a relatively low level of inflammatory activity, the soluble calcification inhibitor fetuin-A could not be identified as an independent predictor of aortic stiffness as measured with PWV and AI.

Determinants of arterial distensibility in patients with renal failure.

BACKGROUND: An increased stiffness of the arterial system is an adverse risk factor for the outcome in patients with renal disease. Few studies have focused on the determinants of an increased arterial stiffness in patients with renal failure. As the percentage of patients with renal failure secondary to vascular disease and/or diabetes mellitus is rapidly growing, and the underlying disease per se may also influence the arterial wall properties, it may also be of interest to study the arterial wall properties in relation to the etiology of kidney disease. METHODS: The distensibility coefficient (DC) of the common carotid artery was used as a marker of arterial stiffness. One hundred and seventeen patients were studied: 47 patients (aged 63 +/- 10 years) with renal failure secondary to vascular disease and/or diabetes mellitus and 70 patients (aged 57 +/- 13 years) with other diagnoses. The origin of the renal failure was retrieved from the patients' charts. RESULTS: Age, mean arterial pressure, and serum calcium level were each independent predictors of arterial stiffness (DC). The DC was significantly lower in the patients with vascular renal disease or diabetes mellitus [11.0 +/- 5.5 (1/MPa)] as compared with patients with renal/urological diseases [15.4 +/- 7.5 (1/MPa)]. Nevertheless, after correction for potentially confounding variables, the relation between cause of renal disease and DC lost significance in the overall group, but remained significant (p < 0.05) in the younger age groups (

Arterial wall properties in patients with renal failure.

Hemodialysis (HD) patients commonly show abnormalities of the arterial system. Only a few studies have focused on arterial wall properties in patients with early stages of renal insufficiency and patients on peritoneal dialysis (PD) therapy. In this study, the distensibility coefficient (DC), a marker of arterial stiffening and intima media thickness (IMT) of the common carotid artery (CCA) and a surrogate marker of atherosclerosis, was assessed in four age-matched groups of patients: 18 HD patients, 36 PD patients, 30 patients with chronic renal failure (CRF) not yet on dialysis therapy with a creatinine clearance (CCl) between 10 and 70 mL/min, and 25 normotensive controls with normal renal function. Arterial wall properties were assessed by an automated vessel wall detection system. In patients with CRF and HD patients, but not PD patients, the DC of the CCA was significantly reduced (P < 0.05) compared with controls (CRF, 12.6 +/- 7.5 10(-3)/kPa; HD, 11.6 +/- 7.6 10(-3)/kPa; and PD, 14.7 +/- 6.2 10(-3)/kPa compared with controls, 16.7 +/- 4.6 10(-3)/kPa). In patients with CRF, a significant relationship was found between CCl and the DC (r = 0.41; P = 0.02). IMT was not different among patients with CRF (589 +/- 115 microm), HD (622 +/- 115 microm) and PD patients (585 +/- 121 microm), and controls (668 +/- 150 microm). In conclusion, compared with controls, the DC of the CCA was significantly reduced in HD patients and those with CRF, but not PD patients. In patients with CRF, the DC correlated significantly with CCl. IMT did not differ between groups of renal patients and controls.