Curcumin, as a pleiotropic agent, improves doxorubicin-induced nephrotic syndrome in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Curcumin, a phenolic compound extracted from the rhizome of turmeric (Curcuma longa L.), has been reported to have broad biological functions including potent antioxidant and renoprotective effects. It has been reported that Curcumin has a certain protective effect on the kidney. However, its mechanism of action needs further study. AIM OF THE STUDY: The present research aims at investigating the therapeutic effects and its underlying mechanism of curcumin on NS. MATERIALS AND METHODS: The conditionally immortalized mouse podocyte cell line was utilized to evaluate the podocyte-protective effect of curcumin and its effects on NF-κB pathway and Nrf2/ARE pathway in podocyte in vitro. Furthermore, the DOX-induced NS rats were utilized to investigate the therapeutic effects and its underlying mechanism of curcumin against NS in vivo. RESULTS: The consequences of this study revealed that curcumin activated Nrf2, inhibited NF-κB pathway and up-regulated podocin in DOX-induced podocyte. Further research results showed that curcumin can considerably alleviate proteinuria and improve hypoalbuminemia in NS rats, and lower blood lipid levels to alleviate hyperlipidemia in NS rats, indicating that curcumin has significant therapeutic effects on rat NS. Further observation by electron microscopy and detection showed that curcumin can improve renal function and podocyte injury, which may be related to the repairment of mRNA expression and podocin protein. Interestingly, the results of the blood rheology test showed that curcumin can effectively reduce whole blood viscosity (WBV) and plasma viscosity (PV), and reduce hematocrit (Hct). In addition, the oxidative stress state of kidney in NS rats was considerably reversed by curcumin, which may be achieved by activating Nrf2 and increasing the expression of antioxidant enzymes HO-1, NQO-1. We also found that NF-κB pathway is activated in the kidney of NS rats, and curcumin can inhibit the activation of NF-κB by down-regulating the expression of NF-κB p65, reducing the level of p-IκBα and up-regulating the expression of IκBα. CONCLUSION: These findings suggest that curcumin, as a multifunctional agent, exerts a protective effect on DOX-induced nephrotic syndrome in rats, which provides a pharmacological basis for the further development of curcumin and also provides a basis for the advantages of multi-targeted drugs in the processing of NS.

Round Table Discussion.

The 1st International Carnitine Working Group concluded with a round table discussion addressing several areas of relevance. These included the design of future studies that could increase the amount of evidence-based data about the role of carnitine in the treatment of fatty acid oxidation defects, for which substantial controversy still exists. There was general consensus that future trials on the effect of carnitine in disorders of fatty acid oxidation should be randomized, double-blinded, multicentered and minimally include the following diagnoses: medium-chain acyl coenzyme A (CoA) dehydrogenase deficiency, very long-chain acyl-CoA dehydrogenase deficiency, long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency and mitochondrial trifunctional protein deficiency. Another area that generated interest was trials of carnitine in cardiomyopathy and, especially, the use of biomarkers to identify patients at greater risk of cardiotoxicity following treatment with anthracyclines. The possibility that carnitine treatment may lead to improvements in autistic behaviors was also discussed, although the evidence is still not sufficient to make any firm conclusions in this regard. Preliminary data on carnitine levels in children and adolescents with primary hypertension, low birth weight and nephrotic syndrome was also presented. Lastly, the panelists stressed that there remains an objective need to harmonize the terminology used to describe carnitine deficiencies (e.g., primary, secondary and systemic deficiency).

Zinc supplement in reduction of relapses in children with steroid sensitive nephrotic syndrome.

OBJECTIVE: To determine whether Zinc supplementation could reduce relapse rate in children with nephrotic syndrome. STUDY DESIGN: Randomized-controlled trial. PLACE AND DURATION OF STUDY: National Institute of Child-Health and The Kidney Centre, Karachi, from January 2008 to June 2009. METHODOLOGY: Sixty nephrotic children aged 2 - 15 years were selected. Baseline data including age, number of infections and relapses during pre and post study one year were recorded. Randomization was done to divide into Zinc group (Zg) to receive Zinc versus placebo (Pg) for 6 months. Relapses and infections were treated with standard therapy. T-test and chi-square tests were used to compare the mean values and proportions respectively with significance at p < 0.05. RESULTS: Among 60 children, 54 completed trial (Zg = 25, Pg = 29). Forty (74%) were males and 14 (26%) females. Mean age, pre study relapses and Zinc level in the two groups were similar. Overall, infections and relapses were observed in 43 (79.62%) and 17 cases (31.48%) respectively. There was no significant difference in frequency of infections and mean infection rate in Zg (20, 80% and 1.92 ± 1.47) compared to Pg (23, 79.3% and 2 ± 1.53, p = 0.950). Relapses occurred in 7 (28%) in Zg compared to 10 (34%) in Pg which was not significant (p = 0.609). Mean infection and relapse rate per patient per year (PPPY) in Zg was 1.92 ± 1.47and 1.14 ± 0.37 compared to 2 ± 1.53 and1.3 ± 0.48 in Pg respectively (p=0.846, 0.464). Pre study relapses in two groups were similar (Zg vs. Pg = 96 vs. 96.6%) whereas post study relapses in Zg were lower (7, 28%) compared to Pg (10, 34.5%). Post study mean relapse rate in Zg was 1.14 ± 0.37 PPPY compared to 2.71 ± 1.11 in pre study (p = 0.005). In Pg, post study mean relapse rate PPPY was 1.30 ± 0.48 compared to 1.70 ± 0.48 in pre study period (p = 0.037). Relapse rate reduction was 43% after Zinc supplementation compared to 27% reduction in placebo. Metallic taste was observed in 10% of cases. CONCLUSION: Zinc supplementation was helpful in reducing relapses in nephrotic syndrome.

Efficacy of zinc supplements in reducing relapses in steroid-sensitive nephrotic syndrome.

Relapses in steroid-sensitive nephrotic syndrome (SSNS) often follow infections of the respiratory or gastrointestinal tract. Based on data that zinc supplements reduce the risk of infections, we examined the efficacy of such supplements in reducing relapse rates in these patients. Eighty-one patients with SSNS (1-16 years old) were stratified into frequent (n = 52) and infrequent (n = 29) relapsers and randomized to receive 12-months of therapy with the recommended dietary allowance of zinc (10 mg/day) (n = 40) or placebo (n = 41). Patients with frequent relapses also received long-term, alternate-day prednisolone. Subjects receiving zinc showed a 20% lower frequency of relapses, with 44.7% of the patients having sustained remission compared to 27.5% in the placebo group (P > 0.05). Patients with frequent relapses receiving zinc showed a 28% reduction in relapse rates and a significantly higher likelihood of sustained remission (P = 0.02). Findings from this double blind, randomized study suggest that zinc supplementation results in trends towards remission and reduced relapses, especially in patients with frequent relapses. Prospective, adequately powered studies are required for confirmation of these findings.

Amelioration of anti-cancer agent adriamycin-induced nephrotic syndrome in rats by Wulingsan (Gorei-San), a blended traditional Chinese herbal medicine.

Anti-cancer agent adriamycin (ADR) has demonstrated high anti-tumor efficacy. However, its use in chemotherapy has been limited largely due to its diverse toxicities, including renal toxicity, such as nephrotic syndrome with proteinuria. Podocyte injury leads to glomeruli proteinuria. Wulingsan (WLS) is a blended traditional Chinese herbal medicine specifically used for various kidney diseases. In the present study, we found that a water extract of WLS (480 mg/kg, p.o., x 28 days) reduced ADR-induced increase in urine protein excretion, plasma total cholesterol and triglyceride, and decrease in plasma total protein and albumin in rats. Furthermore, the results of electron microscopy demonstrated suppression by WLS of ADR-induced increase in width of foot process, increase in surface density and decrease in volume density. These results suggest that WLS ameliorates ADR-induced proteinuria and podocyte injury. Gene analysis results demonstrated a suppression of renal overexpression of nephrin mRNA and protein by WLS. Radioimmunoassay showed that WLS suppressed ADR-induced increased renal angiotensin II content in rats. Thus our results demonstrate that WLS ameliorates ADR-induced nephrotic syndrome in rats possibly by suppressing ADR-induced hyperactivity of renal renin-angiotensin system to modulate renal nephrin gene expression, thereby protecting podocyte from injury.

The treatment of relapsing primary nephrotic syndrome in children.

OBJECTIVE: To explore better therapy and reduce the rate of re-relapse of primary nephritic syndrome in children who had been treated with corticosteroids but relapsed. METHODS: Eighty relapsers were enrolled from Jan. 1994 to Apr. 2000, who were randomly divided into two groups. The treatment group (n=39) had been treated with tripterysium glucosides for three months, with the control group (n=41) members were treated with cyclophosphmide (CTX) by intermission intravenous pulse, with total dose of CTX not being more than 150 mg/kg. Prednisone, meanwhile, was given to both groups. The total treatment period of prednisone was prolonged by 12-18 months. RESULTS: After following up for 3-7 years, the re-relapse rates of both groups were observed. The re-relapse rate of the treatment group was 28.2% to 29.3% in the CTX-controlled group. The re-relapse rates between two groups were almost similar, and with no observed significant difference (P>0.05). The side effect of tripterysium glucosides was less than that of CTX. CONCLUSION: For the treatment of relapsing nephritic syndrome in children, the combination of tripterysium glucosides and prolonged corticosteroid therapy is as effective as the regimen of CTX plus prolonged use of prednisone.

[Standard versus long-term prednisolone with sairei-to for initial therapy in childhood steroid-responsive nephrotic syndrome: a prospective controlled study].

The most appropriate initial treatment for children with steroid-responsive nephrotic syndrome is controversial. Initial treatment with 18-week prednisolone and the Chinese herbal medicine. Sairei-to, may prevent subsequent relapse. To determine whether similar results can be obtained with a combination of just initial 8-week prednisolone and Sairei-to, we compared the effects of such treatment with those of treatment with 18-week prednisolone and Sairei-to in 196 children with steroid-responsive nephrotic syndrome. The patients were randomly assigned to receive 8-week (group 1) or 18-week (group 2) prednisolone for the initial therapy. All patients received Sairei-to for 2 years in addition to prednisolone. Eighty-eight of the 98 patients in group 1 and 83 of the 98 patients in group 2 completed their trial. At entry, the two groups of patients did not differ in their clinical and laboratory findings. During the 2-year trial, 62 group 1 patients (70%) and 54 group 2 patients (65%) had relapses, and 19 group 1 patients (21%) and 20 group 2 patients (24%) had frequent relapses. The present study demonstrates that a combination of initial 8-week prednisolone and 2-year Sairei-to is effective in children with steroid-responsive nephrotic syndrome.

Effects of sairei-to on the relapse of steroid-dependent nephrotic syndrome.

Sairei-To (Chai-Ling-Tang) was administered to four patients with steroid-dependent relapsing nephrotic syndrome. It was associated with prednisolone and immunosuppressive agents. Histological diagnosis was minimal change in three patients and mild focal glomerulonephritis in one patient. After the start of Sairei-To administration the relapse was markedly suppressed in three patients but not at all in the other. Although we could consider Sairei-To effective for steroid-dependent nephrotic syndrome in the present study, a larger study is necessary to confirm its efficacy.

Effect of thyroparathyroidectomy and parathyroidectomy on renal function and the nephrotic syndrome in rat nephrotoxic serum nephritis.

Dietary phosphorus restriction (PR) prevents uremia in rats with nephrotoxic serum nephritis (NSN). One possible mechanism by which PR could be protective would be through the suppression of parathyroid hormone. To evaluate this possibility two separate protocols were designed. In the first rats were thyroparathyroidectomized (TPTX) before (n = 11) or 5 wk after (n = 7) NSN induction and compared to sham-operated parathyroid intact rats with NSN (n = 12). At the end of the 23-wk study, intact rats were azotemic, plasma creatinine 3.80+/-0.81 mg/100 ml vs. 0.65+/-0.07 for TPTX rats (P < 0.001). During the study 75% of intact rats died of uremia in contrast to none of the TPTX rats (P < 0.001). Renal histological damage was greatly diminished and calcification prevented in TPTX rats. The proteinuria of the heterologous phase was unaffected, but the protein excretion and hypertriglyceridemia (HTG) of the autologous phase were markedly decreased in the TPTX rats. The degree of HTG and proteinuria had a high positive correlation (P < 0.001). Late TPTX also produced significant decreases in proteinuria and HTG regardless of the degree of azotemia, and prevented azotemia if the plasma creatinine at the time of TPTX was