Urinary Protein Loss Research Articles

Late Conversion Is a Risk Factor for mTOR Inhibitor Induced Proteinuria

Introduction: Recently, mTOR inhibitor base regimen has emerging as a main treatment strategy to avert calcineurin inhibitor induced nephrotoxicity in solid organ transplant patients. Results from different centers have confirmed the beneficial effect of this approach in patients with initial kidney creatinine clearance greater than 40ml/min. However, proteinuria is increasingly noticed as a complication of mTOR inhibitor application. The pathological processes responsible for this adverse effect are not completely understood so far. To see if conversion timing will affect the incidence of proteinuria in these patients, we conduct the following study. Methods: Inclusion criteria: kidney transplant recipients regularly follow-up in our clinic fulfilled the following criteria were recruited into this study: 1, creatinine clearance greater than 40ml/min; 2, daily urine protein loss less than 800mg. Exclusion criteria: patients with multiple organ transplantation, pregnancy, poor compliance or allergy to mTOR inhibitor are excluded. Once included, patients were put on everolimus 1.5mg per day. The dosage of everolimus was adjusted to keep their trough serum level between 3-8ng/ml. Their calcineurin inhibitor was reduced by half initially and tapered to the minimal dose within 2-4 weeks i.e. cyclosporin 25mg/ day or tacrolimus 0.5mg/day. Mycophenolic acid dosage were cut immediately by half and tapered as necessary, while steroid dosage was kept at 5mg per day or less. Graft function, hemogram, daily urine protein and biochemistry data including fasting sugar, liver function and lipid profiles were checked regularly. Results: In total, 18 patients were recruited into this study. After follow-up for 6 months, their creatinine clearance improved from 72.4± 5.6ml/min to 85.3± 9.8ml/min. Further analysis showed that five out of seven patients with transplantation duration longer than one year had aggravated proteinuria, which is defined as increase daily urine protein loss from their baseline level for more than 500mg. In eleven patients with transplantation duration less than one year, none has aggravated proteinuria after receiving everolimus treatment. Other factors such as underlying disease, age, baseline graft function, baseline proteinuria, lipid profiles and fasting sugar were all similar in both groups. Conclusion: In this preliminary study, we found that transplantation duration longer than one year is an important risk factor for the development of proteinuria in patients receiving mTOR inhibitor treatment.

Randomized controlled trial of cholecalciferol supplementation in chronic kidney disease patients with hypovitaminosis D

Hypovitaminosis D is common in chronic kidney disease (CKD). Effects of 25-hydroxyvitamin D replenishment in CKD are not well described. An 8-week randomized, placebo-controlled, double-blind parallel intervention study was conducted in haemodialysis (HD) and non-HD CKD patients. Treatment consisted of 40,000 IU of cholecalciferol orally per week. Plasma 25-hydroxyvitamin D (25-OHD), plasma 1,25-dihydroxyvitamin D (1,25-diOHD), plasma parathyroid hormone (PTH), serum phosphate, ionized serum calcium and serum fibroblast growth factor 23 (FGF-23) were analysed. We also investigated biomarkers related to cardiovascular disease (plasma D-dimer, plasma fibrinogen, plasma von Willebrand factor antigen and activity, plasma interleukin 6, plasma C-reactive protein, blood pressure, aortic augmentation index, aortic pulse wave velocity and 24-h urinary protein loss). Objective and subjective health variables were assessed (muscle function tests, visual analogue scores and Health Assessment Questionnaire). Fifty-two CKD patients with 25-OHD <50 nmol/L at screening were included. Cholecalciferol supplementation led to a significant increase to a median of 155 nmol/L 25-OHD (interquartile range 137-173 nmol/L) in treated patients (n = 25, P < 0.001). In non-HD patients, we saw a significant increase in 1,25-diOHD (n = 13, P < 0.01) and a lowering of PTH (n = 13, P < 0.001). This was not observed in HD patients. Cholecalciferol supplementation caused a significant increase in serum calcium and FGF-23. 25-OHD replenishment was effectively obtained with the employed cholecalciferol dosing. In non-HD patients, it had favourable effects on 1,25-diOHD and PTH. Vitamin D-supplemented patients must be monitored for hypercalcaemia. The present study could not identify significant pleiotropic effects of 25-OHD replenishment.

Early treatment with glucocorticoids or cyclophosphamide retains the slit diaphragm proteins nephrin and podocin in experimental lupus nephritis

Renal podocytes and their slit diaphragms ensure the integrity of renal basement membrane and prevent urinary protein loss. We have previously reported that decreases of the podocyte slit diaphragm proteins nephrin and podocin represent early events in the podocytopathy of lupus nephritis (LN). We asked whether immunosuppressive agents such as glucocorticoids and cyclophosphamide may have direct effects on podocytes. We assessed in New Zealand Black/New Zealand White (NZB/W) F1 LN mice glomerular nephrin and podocin expression and localization by the use of Western blot and immunofluorescence; mRNA levels were measured by real-time polymerase chain reaction (PCR) and renal histology by light and electron microscopy. Early treatment with glucocorticoids and cyclophosphamide halted the histologic alterations associated with LN, preserving podocyte foot processes. Nephrin and podocin protein expression significantly increased in both glucocorticoid and cyclophosphamide groups as early as after three months of therapy. Real-time PCR revealed similar enhancement in nephrin and podocin mRNA levels after three to six months of treatment. This study documents that early treatment in experimental LN with glucocorticoids or cyclophosphamide preserves slit diaphragm proteins in podocytes and halts histological changes of the glomeruli, thus raising the possibility of a direct protective effect of these drugs on podocytes.

The Plasma Permeability Factor in Nephrotic Syndrome: Indirect Evidence in Pediatric Peritoneal Dialysis

Nephrotic syndrome (NS) in children has been associated with a systemic circulating permeability factor. Therefore, once peritoneal dialysis (PD) has been started, peritoneal protein losses should be higher in the nephrotic than in the non-nephrotic population. We compared peritoneal protein losses in children with and without NS on PD. Our retrospective 4-year study analyzed Hispanic patients with NS under PD. Data at dialysis entry and 6 months later were compared. Nutritional support was given according to recommended dietary allowances and recommendations from the Kidney Disease Outcomes Quality Initiative. Clinical and biochemical data were obtained, and 24-hour dialysate and urine samples were collected to measure protein losses. Dialysis dose (Kt/V), daily protein intake (DPI), normalized protein equivalent of nitrogen appearance (nPNA), peritoneal equilibration test (PET), and peritonitis rate were determined. All measurements took place at least 4 weeks after resolution of a peritonitis episode. All patients received automated PD using a HomeChoice PD System cycler (Baxter Healthcare Corporation, Deerfield, IL, USA), with an exchange volume of 1100 mL/m(2) and a dextrose concentration of 1.5% - 2.5%. A control group of non-NS children on PD matched by age and sex were also studied. Data are reported as mean ± standard deviation. Differences between groups were calculated using the Mann-Whitney U-test, and p < 0.05 was considered significant. Each study group consisted of 10 patients [NS patients: 4 boys, mean age of 7.3 ± 4.1 years; control patients: 6 boys, mean age of 7.2 ± 4.7 years (p = nonsignificant)]. In the group with NS, 8 patients were diagnosed by biopsy as having focal segmental glomerulosclerosis, and 2 as having minimal-change disease. At study entry, patients with NS had hourly urinary protein losses of 398 ± 313 mg/m(2) and daily peritoneal protein losses of 3.4 ± 1.9 g/m(2), compared with 29.9 ± 31 mg/m(2) and 1.5 ± 1.1 g/m(2) respectively in the control group (p < 0.05). The same statistical difference was found 6 months later. We observed no statistical differences in PET results, daily exchange volume, and mean dextrose concentration of dialysate. Similarly, no significant between-group differences were observed for Kt/V, DPI, nPNA, and biochemical parameters. Hispanic children with NS on PD show higher peritoneal protein losses than do their control counterparts. Such differences could be secondary to increased peritoneal permeability caused by a systemic permeability factor.

Effects of intermittent and continuous resistance training on proteinuria and hematuria in trained young women

Sir, Following the study of effects of endurance training on proteinuria and hematuria in untrained young females [1], we conducted an investigation surrounding the effects of resistive training (RT) on proteinuria and hematuria in 36 trained (regular practice during prior 2 years) healthy women. They aged 20–25 years (22.19 ± 1.81) with body mass index of 21.8 ± 1.51 kg/m2 and VO2max of 38.4 ± 1.54 mL/kg/min. The participants were randomly assigned into Group A (intermittent RT), Group B (continuous RT) and control Group C (each, n = 12). Two days before the RT program, the participants of Groups A and B met in a training session with the intensity of 20% of one-repetition maximum (1RM), while urine samples were obtained at pre-training1 and post-training1 (0 and 1 h) stages. A1RM is the maximum weight that can be lifted one time with proper technique, which was calculated for each movement in each trainee. The participants performed the training protocol (3 days/week) during 8 weeks with an increasing intensity rate of 5% of 1RM per week from 20 to 55%. Each session consisted of two circuits including seven 2.5-min movements consisting attempts against compression on different organs (breast, arm and foot) and lateral traction. There were 2- and 1-min resting intervals between two circuits and two movements, respectively. Indeed, the total time for each session was 65 min which included: a 10-min light warming up, RT protocol for 47 min and a cool-down exercise for 5–10 min. Group B performed each movement with a constant speed (V = one attempt per 2.5 s), continuously. Group A was asked to do each movement with different speed (2V for 10 and ½V for 20 s), intermittently. The speed of movements was controlled by a metronome. Two days after termination of training workouts, following an effort of 20% of 1RM, similar urine samples were collected as pre-training2 and post-training2 stages. Table 1 shows urinary protein levels at different stages. Table 1 Urinary protein levels of participants at different stagesa A significant increase in all urinary protein levels (mixed type, predominantly albuminuria) was observed compared to basal levels, particularly following RT program (P = 0.02, 0.001 and 0.002 for total protein, albumin and β2 microglobulin, respectively), without any significant difference between the two experimental groups (all P > 0.05). No microscopic hematuria was detected in urine samples (all in luteal phase). It seems that different types of physical training (resistive, endurance, continuous or intermittent) have no preference each other in urinary protein loss [1], however, some studies oppose this finding [2]. In addition, physical training may have a protective effect against exercise-induced hematuria in untrained and trained females. Undoubtedly, further researches regarding this issue are needed.

CUBN as a Novel Locus for End-Stage Renal Disease: Insights from Renal Transplantation

Chronic kidney disease (CKD) is a complex disorder. As genome-wide association studies identified cubilin gene CUBN as a locus for albuminuria, and urinary protein loss is a risk factor for progressive CKD, we tested the hypothesis that common genetic variants in CUBN are associated with end-stage renal disease (ESRD) and proteinuria. First, a total of 1142 patients with ESRD, admitted for renal transplantation, and 1186 donors were genotyped for SNPs rs7918972 and rs1801239 (case-control study). The rs7918972 minor allele frequency (MAF) was higher in ESRD patients comparing to kidney donors, implicating an increased risk for ESRD (OR 1.39, p = 0.0004) in native kidneys. Second, after transplantation recipients were followed for 5.8 [3.8–9.2] years (longitudinal study) documenting ESRD in transplanted kidneys – graft failure (GF). During post-transplant follow-up 92 (9.6%) cases of death-censored GF occurred. Donor rs7918972 MAF, representing genotype of the transplanted kidney, was 16.3% in GF vs 10.7% in cases with functioning graft. Consistently, a multivariate Cox regression analysis showed that donor rs7918972 is a predictor of GF, although statistical significance was not reached (HR 1.53, p = 0.055). There was no association of recipient rs7918972 with GF. Rs1801239 was not associated with ESRD or GF. In line with an association with the outcome, donor rs7918972 was associated with elevated proteinuria levels cross-sectionally at 1 year after transplantation. Thus, we identified CUBN rs7918972 as a novel risk variant for renal function loss in two independent settings: ESRD in native kidneys and GF in transplanted kidneys.

Giardia infection: Protein-losing enteropathy in an adult with immunodeficiency

The case of a 52-year-old woman with a past history of thymoma resection who presented with chronic diarrhea and generalized edema is the focal point of this article. A diagnosis of Giardia lamblia infection was established, which was complicated by protein-losing enteropathy and severely low serum protein level in a patient with no urinary protein loss and normal liver function. After anti-helmintic treatment, there was recovery from hypoalbuminemia, though immunoglobulins persisted at low serum levels leading to the hypothesis of an immune system disorder. Good's syndrome is a rare cause of immunodeficiency characterized by the association of hypogammaglobulinemia and thymoma. This primary immune disorder may be complicated by severe infectious diarrhea secondary to disabled humoral and cellular immune response. This is the first description in the literature of an adult patient with an immunodeficiency syndrome who presented with protein-losing enteropathy secondary to giardiasis.

Effects of Anti-Tumor Necrosis Factor Agents for Familial Mediterranean Fever Patients With Chronic Arthritis and/or Sacroiliitis Who Were Resistant to Colchicine Treatment

Effectiveness of anti-tumor necrosis factor (anti-TNF) agents in colchicine-resistant familial Mediterranean fever (FMF) patients has attracted attention in recent years. We analyzed the effect of anti-TNF agents on clinical findings of colchicine-resistant FMF patients with chronic arthritis and/or sacroiliitis. Data from 10 FMF patients (5 male and 5 female patients: mean age, 30.1 [SD, 8.5] years) with chronic arthritis and/or sacroiliitis who were on anti-TNF agents are reviewed. Frequency of FMF attacks before and after treatment with anti-TNF agents was recorded from hospital files. The effects of the anti-TNF treatment were determined by using the number of tender and/or swollen joints, serum acute phase reactant levels, and Bath Ankylosing Spondylitis Disease Activity Index scores. Change in urine protein loss was also evaluated in patients with amyloidosis. In 6 patients, FMF attacks had been considered to be unresponsive to colchicine, and 4 patients were partial responders before treatment with anti-TNF agents. Mean attack frequency of the patients in the 3 months' period before anti-TNF agent treatment was 3.8 (SD, 3.1). After anti-TNF treatment, in 3 patients, FMF attack frequency decreased, and in the remaining 7 patients, no attack occurred. Serum acute phase reactant levels were decreased significantly at 3 and 6 months after anti-TNF treatment (P < 0.05 for all). After anti-TNF treatment Bath Ankylosing Spondylitis Disease Activity Index scores were also decreased significantly (6.2 [SD], 1.7 vs. 2.1 [SD], 1.7; P = 0.012). In all 3 patients with amyloidosis, urine protein loss decreased without any increase in serum creatinine levels. Anti-TNF treatment can have beneficial effects for controlling FMF attacks in FMF patients with chronic arthritis and/or sacroiliitis.

Antiproteinuric treatment reduces urinary loss of vitamin D-binding protein but does not affect vitamin D status in patients with chronic kidney disease

Vitamin D deficiency is common in chronic kidney disease (CKD). Increased urinary loss of vitamin D binding protein (VDBP), the main transporter of 25-hydroxyvitamin D 3 in the circulation, has been postulated to contribute to vitamin D deficiency in proteinuria. To test this hypothesis we analyzed urinary and plasma levels of VDBP, 25-hydroxyvitamin D 3 and 1,25-dihydroxyvitamin D 3 from proteinuric patients, before and after antiproteinuric interventions. We performed a post-hoc analysis of a clinical trial in CKD patients ( n = 13, creatinine clearance median 60 (range 25–177) ml/min) subjected to the following study periods: washout (no antiproteinuric treatment, 4 weeks), lisinopril 40 mg QD (ACEi, 6 weeks), or indomethacin 75 mg BID (NSAID, 4 weeks) in randomized sequence. Healthy subjects screened for donation ( n = 10) served as controls. Plasma and urine VDBP levels were measured by ELISA, 25-hydroxyvitamin D 3 levels by LC–MS and 1,25-dihydroxyvitamin D 3 levels by radioimmunoassay. In CKD patients urinary VDBP excretion was strongly increased (median (range) 5413 (155–211,027) μg/24 h) as compared to healthy controls (64 (23–111) μg/24 h, p < 0.001). Both NSAID and ACEi significantly decreased urinary VDBP excretion, in proportion to proteinuria reduction. Plasma VDBP, 25-hydroxyvitamin D 3 and 1,25-dihydroxyvitamin D 3 levels, however, were similar between patients and controls and not affected by antiproteinuric intervention. Urinary VDBP excretion is markedly increased in proteinuria and responds to antiproteinuric treatment. Urinary VDBP loss is not associated with plasma VDBP or vitamin D 3 levels, suggesting that urinary loss of VDBP does not affect vitamin D status.

Chronic graft-versus-host disease complicated by nephrotic syndrome

Chronic graft-versus-host disease (cGVHD) is one of the most frequent and serious complications of allogeneic hematopoietic stem cell transplantation (HSCT). Nephrotic syndrome (NS) is an uncommon and underrecognized manifestation of cGVHD. We report a patient who developed NS 18 months after allogeneic bone marrow transplantation. The onset of NS was accompanied by active manifestations of cGVHD, and immunosuppressants had not been tapered recently. Renal biopsy revealed membranous nephropathy. The patient failed to improve with three combined immunosuppressants (prednisolone, cyclosporine, and mycophenolate mofetil), but achieved partial remission after intravenous immunoglobulin (IVIG) infusion. Twenty-four months after the diagnosis of NS, the patient was still in hematological remission, with normal serum creatinine level, urinary protein loss of 0.7–1.9 g/day and mild oral mucositis. Our report suggests that NS can be a cGVHD-related immune disorder in HSCT patients. Monitoring of renal parameters, especially proteinuria, is important in cGVHD patients. Our case indicated that post-transplant NS, occurring without history of tapering or following immunosuppressant withdrawal, presents a more severe activity of cGVHD and a relatively severe clinical course. IVIG may modify and control the refractory GVHD-related NS, and can be one of the choices of treatment.

Profound Urinary Protein Loss and Acute Renal Failure Caused by Cyclooxygenase-2 Inhibitor

Cumulative evidence has shown that nonsteroidal anti-inflammatory drugs (NSAIDs) can induce acute renal failure and nephrotic-range proteinuria. Cyclooxygenase-2 (COX-2) inhibitors have less nephrotoxicity; however, recent data indicate that they may cause the same renal problems as NSAIDs do. Herein, we present a case of celecoxib-associated minimal change disease (MCD) with profound urinary protein loss and acute renal failure. Renal function and nephrotic syndrome in this patient resolved completely after discontinuation of celecoxib and treatment with methylprednisolone. Clinicians should keep high index of suspicions in patients developing nephrotic syndrome and acute renal failure after taking COX-2 inhibitors since secondary MCD responds well to timely cessation of COX-2 inhibitors and administration of steroid therapy.

Podocyte main slit diaphragm proteins, nephrin and podocin, are affected at early stages of lupus nephritis and correlate with disease histology

Renal podocytes and their slit diaphragms ensure the integrity of the renal basement membrane that forms the barrier to urinary protein loss. A putative disruption of the slit diaphragm and its main protein components, nephrin and podocin, may be implicated in the pathogenesis of lupus nephritis (LN). We studied the glomerular protein expression of nephrin and podocin in NZB/W LN mice by Western blot and immunofluorescence; mRNA levels were measured by real-time PCR. Human kidney biopsies of class II (n = 5), IV (n = 4), V (n = 7) LN were evaluated for nephrin expression by immunohistochemistry. Glomerular protein expression of nephrin and podocin were significantly reduced in NZB/W LN, starting from the earlier stages (mild mesangial LN) and becoming pronounced at advanced histological forms (focal and diffuse proliferative LN). Nephrin and podocin mRNA levels were substantially decreased in diffuse proliferative disease. Decreased expression of both proteins correlated with electron microscopy findings of distorted slit diaphragms. In patients with LN, nephrin was decreased particularly in diffuse proliferative LN. The main slit diaphragm proteins, nephrin and podocin, are affected from the earlier stages of LN and their expression correlates with disease histology. Our findings suggest a novel role of podocytes and their structures in immune-mediated nephritis.

Receptor-Mediated Endocytosis Is a Trojan Horse in Light-Chain Nephrotoxicity

Receptor-Mediated Endocytosis Is a Trojan Horse in Light-Chain Nephrotoxicity

Renal TRPathies

Many ion channels and transporters are involved in the filtration, secretion, and resorption of electrolytes by the kidney. In recent years, the superfamily of transient receptor potential (TRP) ion channels have received deserved attention because mutated TRP channels are linked to human kidney diseases. This review focuses on two TRP members--TRPC6 and TRPM6--and their functions in the kidney. Gain-of-function mutations in TRPC6 are the cause for progressive kidney failure with urinary protein loss such as FSGS. Thus, TRPC6 is an essential signaling component in a functional slit diaphragm formed by podocytes around the glomerular capillaries. Loss-of-function mutations in TRPM6 are a molecular cause of hypomagnesemia with secondary hypocalcemia, suggesting that TRPM6 is critically involved in transcellular Mg2+ transport in the kidney. Here, we highlight how recent studies analyzing function and expression of these channels in the kidney improve our mechanistic understanding of TRP channel function in general and pave the way to new, promising therapeutic strategies to target kidney diseases such as FSGS and hypomagnesemia with secondary hypocalcemia.

Syncope

Pulmonary embolism is a very infrequent event in previously healthy children, particularly in the outpatient scenario. This report involves a 7-year-old girl who presented to the emergency room after syncope. A prompt diagnostic workup showed a massive pulmonary embolism. A timely treatment initiation permitted a good and rapid response. She represented a diagnostic and treatment challenge, mainly because of the atypical presentation and the absence of known risk factors. Finally, a thorough study uncovered a nephrotic-range urine protein loss. At the beginning, the patient did not meet the whole nephrotic syndrome diagnostic requirements. The complete thombophilic study was normal. The clinical presentation, epidemiology, diagnostic tools and the treatment of pulmonary embolism are reviewed. We also discuss a recently described risk factor, present in our patient, as a potential role in the development of pulmonary embolism.

The use of pooled vs serial urine samples to measure urine protein:creatinine ratios

Evaluation of serial urine protein:creatinine (UPC) ratios is important in prognosticating chronic kidney disease and monitoring response to therapeutic interventions. Owing to random biologic variation in dogs with stable glomerular proteinuria, multiple determinations of UPC ratios often are recommended to reliably assess urine protein loss. This can be cost-prohibitive. The purpose of this study was to evaluate agreement between the mean of 3 UPC ratios obtained on 3 separate urine samples per dog and a single UPC ratio obtained when aliquots of the separate samples were pooled and analyzed as 1 sample. Three separate urine samples were collected from each of 25 dogs, both client-owned and members of a research colony. Protein and creatinine concentrations were measured in the supernatant of each sample using a biochemical analyzer, and the mean of the 3 UPC ratios was calculated. A 1.0 mL aliquot of each of the 3 samples from each dog was pooled to create a fourth sample for that dog, and the UPC ratio of the pooled sample was similarly determined. Agreement and correlation between the mean and pooled UPC ratios were assessed using Bland-Altman difference plots and regression analysis, respectively. The UPC ratio in the pooled samples was highly correlated (r=.9998, P<.0001) with the mean UPC ratio of the 3 separate samples. Strong agreement between results was demonstrated; a UPC ratio from a pooled sample was at most +/-20% different than the mean UPC ratio obtained from 3 separate samples. Measuring the UPC ratio in a pooled sample containing equal volumes of several different urine specimens from the same dog provides a reliable and cost-effective alternative to assessing multiple UPC ratios on several specimens from the same dog.

Role of reactive oxygen species in pathogenesis of nephrotic syndrome

Nephrotic syndrome is the common chronic disorder characterized by alteration of permeability of the glomerular capillary wall, resulting in its inability to restrict the urinary loss of proteins. Nephrotic syndrome is characterized by heavy proteinuria, hypoalbuminemia, hyperlipidemia associated with peripheral edema. The molecular basis of glomerular permselectivity remains largely unknown. In recent years it has been proposed that Nephrotic syndrome is a consequence of an imbalance between oxidant and antioxidant activity. The present study was aimed to test that the reactive oxygen species are the mediators of excessive protein permeability and other complications of Nephrotic syndrome. For this 30 adults with Nephrotic syndrome were studied. The control group comprised 30 healthy adults matched for age. Serum levels of lipid peroxides, nitric oxide (NO⊙), α- tocopherol, ascorbic acid, erythrocyte superoxide dismutase activity, serum albumin, uric acid, cholesterol and plasma total antioxidant capacity were measured. Student's 't' test was applied for statistical analysis. There was a significant increase in lipid peroxide (1.58 ± 0.42 in controls, 3.64 ±1.3 in patients) (P<0.001) levels in study group as compared with controls. α-tocopherol (12.95 ± 1.04 in controls, 9.93 ± 1.43 in patients) (P<0.001), erythrocyte SOD activity(1.88 ± 0.9 in controls 1.07 ± 0.5 in patients) (P=0.01), serum albumin(4.06 ± 0.50 in controls, 3.04 ± 0.11 in patients) (P<0.001), and plasma total antioxidant capacity (847.33 ± 126.83 in controls, 684.00±102.94 in patients) (P<0.001) were significantly decreased. There was non-significant increase in uric acid (P>0.05), a non-significant decrease in NO⊙ (38.48 ± 15.47 in controls 37.47 ± 14.27 in patients) (P>0.05) and ascorbic acid levels ascorbic acid,( 0.95 ± 0.31in controls 0.79 ± 0.30 in patients) (P>0.05) in study group as compared with controls. Imbalance between oxidants and antioxidants may contribute to pathogenesis of proteinuria and related complications in nephrotic syndrome.

Avaliação da relação proteína-creatinina urinária em gatos com doença renal crônica

Doença renal crônica (DRC) é a forma mais comum de doença renal em gatos. Vários fatores têm sido citados como importantes na progressão da doença, dentre eles a proteinúria. A relação proteína-creatinina (RPC) urinária em uma única amostra de urina apresenta boa correlação com a perda de proteína urinária em 24 horas. O objetivo dessa investigação foi determinar a RPC urinária em gatos com DRC adquirida naturalmente. A determinação da RPC foi realizada em nove gatos saudáveis (Grupo I) e em trinta gatos com DRC (Grupo II). Os gatos do Grupo I apresentaram RPC de 0,16±0,10 e os gatos do Grupo II apresentaram RPC de 0,53± 0,59. No Grupo II encontrou-se correlação positiva e significante da RPC com o nível de creatinina sérica. Os resultados deste estudo demonstram que a RPC urinária em gatos com DRC é bastante variável e que, à semelhança do que já havia sido previamente descrito, aproximadamente um terço dos gatos com DRC são considerados proteinúricos segundo critérios estabelecidos pela literatura (RPC urinária &gt;0,4).

Management of patients with nephrotic syndrome.

Nephrotic syndrome is characterised by proteinuria >3.5 g/24h, oedema, hypoalbuminaemia and hyperlipidaemia. Several glomerular diseases, either primary or secondary, may lead to nephrotic syndrome. Investigations for nephrotic syndrome include immunological and infectious evaluations. Renal biopsy is often mandatory, except in diabetes. Depending on aetiology specific treatment, often with immunosuppressive agents, may be implemented. In any cases nonspecific treatment should be started with ACE inhibitors or ARBs. Urinary protein loss leads to several complications: water and sodium retention, hyperlipidaemia, increased risk of thromboembolism and infection, anaemia and alteration of mineral metabolism. Each of these complications must be identified.

Management of patients with nephrotic syndrome.

Nephrotic syndrome is characterised by proteinuria >3.5 g/24h, oedema, hypoalbuminaemia and hyperlipidaemia. Several glomerular diseases, either primary or secondary, may lead to nephrotic syndrome. Investigations for nephrotic syndrome include immunological and infectious evaluations. Renal biopsy is often mandatory, except in diabetes. Depending on aetiology specific treatment, often with immunosuppressive agents, may be implemented. In any cases nonspecific treatment should be started with ACE inhibitors or ARBs. Urinary protein loss leads to several complications: water and sodium retention, hyperlipidaemia, increased risk of thromboembolism and infection, anaemia and alteration of mineral metabolism. Each of these complications must be identified.