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Renal AND Proteinuria [keywords]
- Proteinuria and clinical outcome in CHD patients. [JOURNAL ARTICLE]
- Cardiol Young 2014 Aug 28.:1-6.
Introduction: CHD patients, especially those with associated hypoxaemia, usually have some level of renal function impairment, even though they are relatively young. The aim of the study was to evaluate those clinical and analytical factors that may contribute to microalbuminuria and determine the association of 24-hour proteinuria with thrombotic events and mortality. Methods: A total of 251 CHD patients were studied and demographic characteristics, blood test, and 24-hour urinalysis were analysed. Results: Of the patients, 221 were non-hypoxaemic, and 30 were hypoxaemic (oxygen saturation of 84.3±5.9%). Of the non-hypoxaemic patients, 30 (13.6%), and of the hypoxaemic patients 9 (30%), showed proteinuria (>0.15 g/24 hours) (p=0.028). Hypoxaemic CHD patients also showed higher haematocrit (%) (50.7 (34.6; 72.1) versus 42.8 (34.6; 48.9), p<0.001), serum creatinine (mg/dl) (1.07±0.2 versus 0.96±1.9, p=0.004), microalbuminuria (mg/dl/24 hours) (1.2 (0.0; 261.5) versus 0.5 (0.0; 4.37), p<0.001), proteinuria (gr/24 hours) (1.0 (0.4; 3.1) versus 0.08 (0.04; 0.52), p=0.043), and N-terminal pro-B-type natriuretic peptide (pg/ml) (417.8 (35.7; 8534.0) versus 44.9 (0.0; 670.5), p<0.001) concentrations than non-hypoxaemic CHD patients. During a median follow-up of 26.0 (16.9; 57.7) months, five patients died - one patient had 24-hour proteinuria and four patients did not (p=0.581) - and three patients had some type of thrombosis - two patients had 24-hour proteinuria and one patient did not (p=0.014). Kaplan-Meier survival analysis showed no significant difference between CHD patients with and without 24-hour proteinuria (p=0.631). Conclusion: CHD patients with proteinuria have significantly more thrombosis and more hypoxaemia than those patients without proteinuria.
- Effect of Poria cocos on Puromycin Aminonucleoside-Induced Nephrotic Syndrome in Rats. [Journal Article]
- Evid Based Complement Alternat Med 2014.:570420.
Nephrotic syndrome is associated with altered renal handling of water and sodium and changes in the levels of aquaporins (AQPs) and epithelial Na channels (ENaCs). The dried sclerotia of Poria cocos Wolf (WPC) have been used for treating chronic edema and nephrosis. We evaluated the effects of WPC on puromycin aminonucleoside- (PAN-) induced renal functional derangement and altered renal AQP2 and ENaC expression. In the nephrotic syndrome rat model, animals were injected with 75 mg/kg PAN and then treated with Losartan (30 mg·kg(-1) ·day(-1)) or WPC (200 mg·kg(-1) ·day(-1)) for 7 days. In the WPC group, proteinuria and ascites improved significantly. Plasma levels of triglyceride, total cholesterol, and low-density lipoprotein- (LDL-) cholesterol reduced significantly in the WPC group. In addition, the WPC group exhibited attenuation of the PAN-induced increase in AQP2 and ENaC α/β subunit protein and mRNA levels. WPC suppressed significantly PAN-induced organic osmolyte regulators, reducing serum- and glucocorticoid-inducible protein kinase (Sgk1) and sodium-myo-inositol cotransporter (SMIT) mRNA expression. Our results show that WPC improves nephrotic syndrome, including proteinuria and ascites, through inhibition of AQP2 and ENaC expression. Therefore, WPC influences body-fluid regulation via inhibition of water and sodium channels, thereby, improving renal disorders such as edema or nephrosis.
- Dietary Resistant Starch Prevents Urinary Excretion of Vitamin D Metabolites and Maintains Circulating 25-Hydroxycholecalciferol Concentrations in Zucker Diabetic Fatty Rats. [JOURNAL ARTICLE]
- J Nutr 2014 Aug 27.
Type 2 diabetes (T2D) is the leading cause of nephropathy in the United States. Renal complications of T2D include proteinuria and suboptimal serum 25-hydroxycholecalciferol (25D) concentrations. 25D is the major circulating form of vitamin D and renal reabsorption of the 25D-vitamin D-binding protein (DBP) complex via megalin-mediated endocytosis is believed to determine whether 25D can be activated to 1,25-dihydroxycholecalciferol (1,25D) or returned to circulation. We previously demonstrated that excessive urinary excretion of 25D-DBP and albuminuria occurred in rats with type 1 diabetes (T1D) and T2D. Moreover, feeding rats with T1D high-amylose maize partially resistant to digestion [resistant starch (RS)] prevented excretion of 25D-DBP without significantly affecting hyperglycemia.We used Zucker diabetic fatty (ZDF) rats, a model of obesity-related T2D, to determine whether feeding RS could similarly prevent loss of vitamin D and maintain serum 25D concentrations.Lean control Zucker rats (n = 8) were fed a standard semi-purified diet (AIN-93G) and ZDF rats were fed either the AIN-93G diet (n = 8) or the AIN-93G diet in which cornstarch was replaced with RS (550 g/kg diet; 35% resistant to digestion) (n = 8) for 6 wk.RS attenuated hyperglycemia by 41% (P < 0.01) and prevented urinary DBP excretion and albuminuria, which were elevated 3.0- (P < 0.01) and 3.6-fold (P < 0.01), respectively, in control diet-fed ZDF rats. Additionally, urinary excretion of 25D (P = 0.01) and 1,25D (P = 0.03) was higher (89% and 97%, respectively), whereas serum 25D concentrations were 31% lower (P < 0.001) in ZDF rats fed the control diet compared with RS-fed ZDF rats. Histopathologic scoring of the kidney revealed that RS attenuated diabetes-mediated damage by 21% (P = 0.12) despite an ∼50% decrease in megalin protein abundance.Taken together, these data provide evidence that suggests vitamin D balance can be maintained by dietary RS through nephroprotective actions in T2D, which are independent of vitamin D supplementation and renal expression of megalin.
- Novel INF2 mutations in an Italian cohort of patients with focal segmental glomerulosclerosis, renal failure and Charcot-Marie-Tooth neuropathy. [Journal Article]
- Nephrol Dial Transplant 2014 Sep.:iv80-iv86.
Mutations of INF2 represent the major cause of familial autosomal dominant (AD) focal segmental glomerulosclerosis (FSGS). A few patients present neurological symptoms of Charcot-Marie-Tooth (CMT) disease but the prevalence of the association has not been assessed yet.We screened 28 families with AD FSGS and identified 8 INF2 mutations in 9 families (32 patients overall), 3 of which were new. Mutations were in all cases localized in the diaphanous-inhibitory domain (DID) of the protein.Clinical features associated with INF2 mutations in our patient cohort included mild proteinuria (1.55 g/L; range 1-2.5) and haematuria as a unique symptom that was recognized at a median age of 21.75 years (range 8-30). Eighteen patients developed end-stage renal disease during their third decade of life; 12 patients presented a creatinine range between 1.2 and 1.5 mg/dL and 2 were healthy at 45 and 54 years of age. CMT was diagnosed in four cases (12.5%); one of these patients presented an already known mutation on exon 2 of INF2, whereas the other patients presented the same mutation on exon 4, a region that was not previously associated with CMT.We confirmed the high incidence of INF2 mutations in families with AD FSGS. The clinical phenotype was mild at the onset of the disease, but evolution to ESRD was frequent. The incidence of CMT has, for the first time, been calculated here to be 12.5% of mutation carriers. Our findings support INF2 gene analysis in families in which renal failure and/or neuro-sensorial defects are inherited following an AD model.
- Alport syndrome from bench to bedside: the potential of current treatment beyond RAAS blockade and the horizon of future therapies. [REVIEW]
- Nephrol Dial Transplant 2014 Sep; 29(suppl 4):iv124-iv130.
The hereditary type IV collagen disease Alport syndrome (AS) always leads to end-stage renal failure. Yesterday, for the past 90 years, this course was described as 'inevitable'. Today, RAAS blockade has changed the 'inevitable' course to a treatable disease. Tomorrow, researchers hope to erase the 'always' from 'always leads to renal failure' in the textbooks. This review elucidates therapeutic targets that evolve from research: (i) kidney embryogenesis and pathogenesis; (ii) phenotype-genotype correlation and the role of collagen receptors and podocytes; (iii) the malfunctioning Alport-GBM; (iv) tubulointerstitial fibrosis; (v) the role of proteinuria in pathogenesis and prognosis; and (vi) secondary events such as infections, hyperparathyroidism and hypercholesterolaemia. Therefore, moderate lifestyle, therapy of bacterial infections, Paricalcitol in adult patients with hyperparathyroidism and HMG-CoA-reductase inhibitors in adult patients with dyslipoproteinemia might contribute to a slower progression of AS and less cardiovascular events. In the future, upcoming treatments including stem cells, chaperon therapy, collagen receptor blockade and anti-microRNA therapy will expand our perspective in protecting the kidneys of Alport patients from further damage. This perspective on current and future therapies is naturally limited by our personal focus in research, but aims to motivate young scientists and clinicians to find a multimodal cure for AS.
- Gitelman syndrome and glomerular proteinuria: a link between loss of sodium-chloride cotransporter and podocyte dysfunction? [Journal Article]
- Nephrol Dial Transplant 2014 Sep.:iv117-iv120.
We report on a 27-year-old patient presenting with chronic hypokalaemia, inappropriate kaliuresis, hypomagnesaemia and alkalosis, associated with moderate proteinuria. Genetic analysis evidenced a homozygous mutation (p.Arg399Cys) in the SLC12A3 gene coding for the sodium-chloride cotransporter (NCC), confirming the diagnosis of Gitelman syndrome. Further genetic testing did not show any mutation in NPHS2. A renal biopsy was performed in view of the unusual association with proteinuria. Light microscopy showed hypertrophy of the juxtaglomerular apparatus and discrete mesangial thickening. In addition to possible focal segmental glomerular sclerosis lesions, electron microscopy showed extensive segments of variably thickened glomerular basement membrane (GBM), contrasting with segments of regular GBM of low range thickness, and effacement of podocyte foot processes. Of interest, alterations of the GBM were also observed in a Slc12a3 knock-out mouse model for Gitelman syndrome. These data suggest that the association between Gitelman syndrome and secondary changes of the GBM is probably not coincidental. Possible mechanisms include angiotensin II- or renin-induced podocyte lesions, as well as chronic hypokalaemia.
- Renal biopsy in patients over 75: 131 cases. [JOURNAL ARTICLE]
- Clin Nephrol 2014 Aug 27.
Introduction: Demographic analysis shows the ageing of the global population and the consequent increase in the age of hospitalized subjects and of patients starting dialysis. Hence, interest in the feasibility, safety, and usefulness of renal biopsy in elderly patients is growing. We examined the data of 131 patients over the age of 75 who underwent renal biopsy. We analyzed the safety of the procedure, treatment, and outcomes. Results: Histological diagnoses included: membranous glomerulonephritis (GN) 20.6%, crescentic GN 12.9%, IgAGN 10.6%, focal segmental glomerulosclerosis 9.1%, acute GN 4.5%, amyloidosis 9.1%, and acute tubular necrosis 3.8%. Mean glomerular obsolescence was 28.9 ± 27.9%. Mean age of the patients was 78.7 ± 5.73 years. At the time of biopsy, serum creatinine (SCr) was 4.47 ± 2.56 mg/dL and proteinuria was 4.82 ± 6.78 g/day. Targeted treatment was given to 51.9% of patients, 52.9% of whom had a good clinical response. Eight patients had clinically non-relevant side effects (11.7%). A positive response (defined as a more than 50% reduction of SCr, or by partial or complete remission of proteinuria) was observed in 36 patients (52.9%). 76 patients were monitored for 57 ± 9.89 months: 18 patients were on dialysis (follow-up 2.56 ± 3.61 months), 15 died (follow-up 58.5 ± 13.43 months), and 52 remained under nephrologic observation for 36 ± 31 months (SCr was 2.56 ± 0.75 mg/dL and proteinuria was 4.82 ± 6.78 g/day). Conclusion: In our experience, renal biopsy is safe even in very elderly patients; it allowed targeted treatment in 51.9% of patients, 52.9% of whom had a good clinical response, possibly contributing to prolonged patient survival and improved quality of life.
- Pediatric case of crescentic post-streptococcal glomerulonephritis with myeloperoxidase anti-neutrophil cytoplasmic antibody. [JOURNAL ARTICLE]
- Clin Nephrol 2014 Aug 27.
Post-streptococcal glomerulonephritis (PSGN) generally has a good renal prognosis, and immunosuppressive therapies are not needed. However, a few patients present with severe acute kidney injury and extensive crescent formations. The etiology of such patients is not well known, and involvement of anti-neutrophil cytoplasmic antibodies is rarely reported. A 9-year-old girl with rapidly progressive nephritic syndrome was diagnosed with PSGN. A biopsy showed diffuse crescentic glomerulonephritis with immunoglobulin G and C3 deposits; moreover, humps were observed on electron microscopy. After she was administered methylprednisolone pulse therapy and intravenous cyclophosphamide, followed by prednisolone and azathioprine therapy, her urinary abnormalities improved and renal function normalized. However, the myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) titers gradually increased. We speculated that PSGN may be augmented by increased MPO-ANCA levels. Therefore, the patient is currently being treated with losartan, enalapril, azathioprine, and prednisolone. Although the MPO-ANCA titer remains high, urinary findings show mild proteinuria and her renal function has been norma for 18 months since onset. A progressive clinical course and severe histological findings may indicate the involvement of ANCA in deterioration of condition in patients with PSGN. Furthermore, in such cases immunosuppressive therapies should be considered even in pediatric PSGN.
- Management of proteinuria in the transplanted patient. [JOURNAL ARTICLE]
- Pediatr Nephrol 2014 Aug 27.
Proteinuria is a relatively frequent complication in children after renal transplantation (40-80 %). It is usually mild and non-nephrotic in nature and predominantly tubular in origin. The major causes of post-transplant proteinuria are recurrence of primary glomerulonephritis [mostly focal segmental glomerulosclerosis (FSGS)], rejection (acute and chronic), mTOR inhibitors or hypertension. Proteinuria is a risk factor for graft loss and patient death in adults, and even a mild proteinuria (0.1-0.2 g/day) is associated with impaired graft and patient survival. In children, proteinuria seems to be associated with graft but not patient survival. Proteinuria (protein/creatinine ratio) should be assessed regularly in all children. In children with prior chronic kidney disease due to idiopathic FSGS, proteinuria should be assessed daily during the first month after transplantation to enable early diagnosis of recurrence. The cause of proteinuria should be identified, and graft biopsy should be considered in children with unexplained proteinuria, especially with new onset proteinuria or deterioration of previously mild proteinuria. Treatment must be primarily targeted at the cause of proteinuria, and in normotensive children symptomatic antiproteinuric therapy with angiotensin-converting enzyme inhibitors/angiotensin II receptor antagonists should also be initiated. Other antihypertensive drugs should be used to achieve target blood pressure of <75th percentile. Target proteinuria should be <20 mg/mmol creatinine.
- Renal changes in the early stages of diet-induced obesity in ovariectomized rats. [JOURNAL ARTICLE]
- Physiol Res 2014 Aug 26.
The relationship between obesity and renal lesions, especially in low estrogen levels, has been less documented. The aim of this study was to assess the renal changes in diet-induced obesity in ovariectomized rats. Wistar rats were ovariectomized or sham-operated and divided into four groups: sham-operated rats fed a standard diet (SSD); ovariectomized rats fed a standard diet (OSD); sham-operated rats fed a high-fat diet (SHFD); ovariectomized rats fed a high-fat diet (OHFD). Body weight and blood pressure were measured weekly. The rats were killed 24 weeks after initiation of standard or high-fat diet treatment, the kidneys were removed for immunohistochemical and histological studies. Blood and urine samples were collected to quantify sodium, potassium and creatinine. OHFD rats presented increases in visceral adipose tissue, serum insulin levels, blood pressure and proteinuria, and a decrease in fractional excretion of sodium as well. Histological and morphometric studies showed focal alterations in the renal cortex. Expression of macrophages, lymphocytes, nuclear factor-kappa B (NF-kappaB), Proliferating Cell Nuclear Antigen (PCNA), angiotensin II (ANG II) and vimentin was greater in OHFD rats than in control rats. Thus, these results demonstrate that the high-fat diet in ovariectomized rats promoted renal function and structure changes, renal interstitial infiltration of mononuclear cells and increased expression of ANG II and NF-kappaB.