Hyperoxaluria and systemic oxalosis: current therapy and future directions

Excessive urinary oxalate excretion, termed hyperoxaluria, may arise from inherited or acquired diseases. The most severe forms are caused by increased endogenous production of oxalate related to one of several inborn errors of metabolism, termed primary hyperoxaluria. Recurrent kidney stones and progressive medullary nephrocalcinosis lead to the loss of kidney function, requiring dialysis or transplantation, accompanied by systemic oxalate deposition that is termed systemic oxalosis. For most primary hyperoxalurias, accurate diagnosis leads to the use of therapies that include pyridoxine supplementation, urinary crystallisation inhibitors, hydration with enteral fluids and, in the near future, probiotic supplementation or other innovative therapies. These therapies have varying degrees of success, and none represent a cure. Organ transplantation results in reduced patient and organ survival when compared with national statistics. Exciting new approaches under investigation include the restoration of defective enzymatic activity through the use of chemical chaperones and hepatocyte cell transplantation, or recombinant gene therapy for enzyme replacement. Such approaches give hope for a future therapeutic cure for primary hyperoxaluria that includes correction of the underlying genetic defect without exposure to the life-long dangers associated with organ transplantation.     

原发性高草酸尿症导致的移植肾早期肾功能丧失(附1例报告)

目的报道原发性高草酸尿症引起的移植肾功能丧失的病程、肾脏病理改变及其诊治。方法个案报道结合文献综述。结果1例双肾多发性结石导致肾衰的男性患者肾移植术后出现移植肾功能丧失，患者血草酸浓度明显高于对照，移植肾病理发现肾小管内大量结晶形成，手术摘取的肾结石成分证实为草酸钙，最后患者被确诊为原发．性高草酸尿症。结论多发性肾结石的患者要进行原发性高草酸尿症的排查。对该类患者肾移植要谨慎，目前理想的治疗手段是肝肾联合移植。     

Curative treatment with extracts of Bombax ceiba fruit reduces risk of calcium oxalate urolithiasis in rats

Context: Drawbacks of presently available treatments for urolithiasis necessitate finding the treatment of hyperoxaluria specifically aimed at reduction in oxalate excretion. Interestingly, many Indian tribes use Bombax ceiba L. (Bombacaceae) fruits as a traditional medicine for the treatment of urinary stones.

Objective: The present study investigated the efficacy of B. ceiba fruit extracts as curative agents in experimentally induced calcium oxalate urolithiatic rats.

Materials and methods: Calcium oxalate lithiasis was induced in rats by oral administration of 0.75% ethylene glycol for 14 consecutive days. Treatments with aqueous and ethanol extract of B. ceiba fruit (400?mg/kg body weight) was performed in the same manner for further 14 consecutive days. Cystone (750?mg/kg body weight) was used as reference antiurolithiatic drug. The urinary excretion and kidney deposition of offending salt components, and serum biochemical parameters were investigated.

Results: Oral administration of ethylene glycol resulted in hyperoxaluria and increased renal excretion of calcium and phosphate. However, supplementation with aqueous and ethanol extracts of B. ceiba fruit significantly (p?<?0.05) reduced the elevated urinary oxalate, showing a regulatory action on endogenous oxalate synthesis. The increased deposition of stone forming constituents in kidneys of calculogenic rats was also significantly lowered with curative treatment of aqueous and ethanol extract.

Discussion and conclusion: The results indicate that the fruit of B. ceiba is endowed with lithontriptic activity warranting further development for curative treatment of urolithiasis.     

Protective effect of the hydro-alcoholic extract of Rubia cordifolia roots against ethylene glycol induced urolithiasis in rats

This study investigated the protective effect of the hydro-alcoholic extract of roots of Rubia cordifolia Linn. (HARC) against ethylene glycol induced urolithiasis and its possible underlying mechanisms using male Wistar albino rats. Ethylene glycol feeding resulted in hyperoxaluria, hypocalciuria as well as increased renal excretion of phosphate. Supplementation with HARC significantly prevented change in urinary calcium, oxalate and phosphate excretion dose-dependently. The increased calcium and oxalate levels and number of calcium oxalate crystals deposits in the kidney tissue of calculogenic rats were significantly reverted by HARC treatment. The HARC supplementation also prevents the impairment of renal functions.     

Novel therapeutic approaches in primary hyperoxaluria

ABSTRACT

Introduction: Currently, three types of primary hyperoxaluria (PH I–III) are known, all based on different gene-mutations affecting the glyoxylate metabolism in the liver. Disease hallmark is an increased endogenous oxalate production and thus massively elevated urinary excretion of oxalate and other type-specific metabolites. Hyperoxaluria induces the formation of calcium-oxalate kidney stones and/or nephrocalcinosis. In addition to that, a chronic inflammasome activation by hyperoxaluria per se, often leads to an early deterioration of kidney function, regularly resulting in end-stage renal disease (ESRD) at least in patients with type I PH. Except for vitamin B6 treatment in PH I, therapeutic regimen nowadays consists only of supportive measures, like significantly increased fluid intake and medication increasing the urinary solubility like alkaline citrate.

Areas covered: Disease burden can be severe, and both clinicians and scientist are eager in finding new therapeutic approaches. The currently ongoing clinical studies and promising research in this field are reported in this paper. To present a complete overview, we searched electronic databases, like Clinical trial gov, National Center for Biotechnology Information PubMed, congress reports, press releases and personal information acquired at congresses and conventions. Searches were conducted using the following medical headings: (primary) hyperoxaluria, PH, therapy, treatment and research.

Expert opinion: There is light on the horizon that new treatment options will be available in due time, as there are several promising therapeutic agents currently under investigation, some being at the first levels of drug development, but some already in ongoing clinical trials (phase I-III).     

Kidney stones: an update on current pharmacological management and future directions

Introduction: Kidney stones are a common problem worldwide with substantial morbidities and economic costs. Medical therapy reduces stone recurrence significantly. Much progress has been made in the last several decades in improving therapy of stone disease.

Areas covered: This review discusses i) the effect of medical expulsive therapy on spontaneous stone passage, ii) pharmacotherapy in the prevention of stone recurrence and iii) future directions in the treatment of kidney stone disease.

Expert opinion: Fluid intake to promote urine volume of at least 2.5 L each day is essential to prevent stone formation. Dietary recommendations should be adjusted based on individual metabolic abnormalities. Properly dosed thiazide treatment is the standard therapy for calcium stone formers with idiopathic hypercalciuria. Potassium alkali therapy is considered for hypocitraturia, but caution should be taken to prevent potential risk of calcium phosphate stone formation. For absorptive hyperoxaluria, low oxalate diet and increased dietary calcium intake are recommended. Pyridoxine has been shown effective in some cases of primary hyperoxaluria type I. Allopurinol is used in calcium oxalate stone formers with hyperuricosuria. Treatment of cystine stones remains challenging. Tiopronin can be used if urinary alkalinization and adequate fluid intake are insufficient. For struvite stones, complete surgical removal coupled with appropriate antibiotic therapy is necessary.     

New treatments for acute humoral rejection of kidney allografts

Acute antibody-mediated rejection (acute humoral rejection; AHR) of organ allografts usually presents as severe dysfunction with a high risk of allograft loss. Peritubular capillary complement C4d deposition with renal dysfunction, associated with circulating donor-specific anti-human leukocyte antigen alloantibodies, is diagnostic of AHR in kidney allografts. Removal of alloantibodies with suppression of antibody production and rejection reversal is now possible. Therapeutic strategies that include combinations of plasmapheresis (or immunoadsorption), tacrolimus, mycophenolate mofetil and/or intravenous immunoglobulins, as well as rituximab or splenectomy, have been recently used to successfully treat AHR. However, the optimal protocol to treat AHR still remains to be defined. Anti-CD20⁺ monoclonal antibody therapy (rituximab) aiming at depleting B cells and suppressing antibody production has been used as rescue therapy in some episodes of steroid- and antilymphocyte-resistant humoral rejection. Plasmapheresis and/or intravenous polyclonal immunoglobulin, as well as rituximab, have also been used to successfully desensitize selected high-immunological risk patients in anticipation of a previously cross-match positive (or ABO incompatible) kidney transplantation. In the near future, the possible role of new specific anti-B-cell approaches or, possibly, of new anti-T-cell activation approaches using selective agents such as belatacept should be assessed to further refine the present treatment of humoral rejection.     

Liver transplantation for hepatocellular carcinoma: current role and future opportunities

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver. It represents the fifth most common cancer worldwide, and one whose incidence is on the rise. Liver cancer is the third most common cause of cancer mortality globally and thus a major health concern worldwide. Therapeutic options for this tumor include surgical resection, local ablative therapies, and systemic treatment. Liver transplantation has emerged as a highly effective treatment for patients with HCC, particularly in the setting of significant underlying liver disease. Current protocols in transplantation for this tumor utilize strict size criteria and staging (TNM classification) to select patients for this therapy. Selection criteria for liver transplantation for HCC that are accepted in the U.S. include: 1 tumor < 5cm, no greater than three tumor nodules, each less than 3cm in diameter 3) no macroscopic invasion of blood vessels or lymph nodes, and no extra-hepatic spread of tumor. Eligibility criteria and immunosuppression strategies are continuing to evolve in this field. Nonetheless, in appropriately selected patients, liver transplantation may provide a cure for HCC with survival rates equal to that of liver transplantation for end-stage liver disease (ESLD) from other causes. Liver transplantation has been established as one of the principal treatment modalities for this difficult disease.     

Modulatory effects of N-acetylcysteine on hyperoxaluric manifestations in rat kidney

Hyperoxaluria is a condition where excessive oxalate is present in the urine. Many reports have documented free radical generation followed by hyperoxaluria as a consequence of which calcium oxalate deposition occurs in the kidney tissue. The present in vivo study was designed to investigate the potential of N-acetylcysteine in modulating hyperoxaluric manifestation induced by sodium oxalate in the rat kidneys. Male wistar rats in one group were administered single dose of sodium oxalate (70 mg/kg body weight) intraperitoneally to induce hyperoxaluric conditions and in the other group, rats were injected N-acetylcysteine (NAC) (200 mg/kg body weight) intraperitoneally, half an hour after sodium oxalate dose. The treatment is for a period of 24 h. N-acetylcysteine significantly reduced hyperoxaluria caused oxidative stress by reducing lipid peroxidation, restoring antioxidant enzymes activity in kidney tissue, followed by reduction in impairment of renal functioning. In addition, NAC administration reduced the number of calcium oxalate monohydrate (COM) crystals in the urine as observed under polarization microscope. Histological analysis depicted that NAC treatment decreased renal epithelial damage, inflammation and restored normal glomeruli morphology. Thus, it shows that use of an extraneous antioxidant may prove beneficial for combating the conditions of oxidative stress produced by hyperoxaluria.     

Oral administration of oxalate-enriched spinach extract as an improved methodology for the induction of dietary hyperoxaluric nephrocalcinosis in experimental rats

Experimental induction of hyperoxaluria by ethylene glycol (EG) administration is disapproved as it causes metabolic acidosis while the oral administration of chemically synthesized potassium oxalate (KOx) diet does not mimic our natural system. Since existing models comprise limitations, this study is aimed to develop an improved model for the induction of dietary hyperoxaluria, and nephrocalcinosis in experimental rats by administration of naturally available oxalate rich diet. Male albino Wistar rats were divided into five groups. Group I, control; group II rats received 0.75% EG, group III rats fed with 5% KOx diet and group IV and V rats were administered with spinach extract of 250 and 500?mg soluble oxalate/day respectively, for 28 d. Urine and serum biochemistry were analyzed. After the experimental period, rats were sacrificed, liver and kidney tissue homogenates were used for antioxidant and lipid peroxidation assay. Relative change in expression of kidney injury molecule-1 (KIM-1) and crystal modulators genes in kidney tissues were evaluated. Tissue damage was assessed by histology studies of liver and kidney. Experimental group rats developed hyperoxaluria and crystalluria. Urine parameters, serum biochemistry, antioxidant profile, lipid peroxidation levels and gene expression analysis of experimental group II and III rats reflected acute kidney damage compared to group V rats. Histopathology results showed moderate hyperplasia in liver and severe interstitial inflammation in kidneys of group II and III than group V rats. Ingestion of naturally available oxalate enriched spinach extract successfully induced dietary hyperoxaluria and nephrocalcinosis in rats with minimal kidney damage.     

Ethylene glycol induced renal toxicity in female Wistar rats

The calcium oxalate nephrolithiasis due to ethylene glycol treatment has long been observed in male species but the prevalence of calcium oxalate nephrolithiasis in female species due to ethylene glycol has been still a subject of controversy. Ethylene glycol was administered in drinking water at three different doses (0.4%, 0.75% and 1.0%, v/v) for 28 days in female Wistar rats. Ethylene glycol treatment caused significant decrease in body weight and corresponding increase in relative organ weight with significant hypercalciuria, hyperoxaluria and proteinuria as well as increased retention of calcium, oxalate, phosphate and total protein in kidney in a dose — and time — dependent manner. However, calcium level was significantly reduced in the serum while an increase in total protein and phosphate level in serum was observed. Furthermore, there was a significant reduction in magnesium level in urine, serum and kidney due to ethylene glycol. The effects were also confirmed in histopathological studies.     

Control of urinary risk factors of stone formation by Salvadora persica in experimental hyperoxaluria

Urolithiasis, the process of formation of stones in the kidneys and urinary tract, is the major clinical manifestation of hyperoxaluria. Ethylene glycol feeding resulted in hyperoxaluria with increased renal excretion of oxalate, sodium, calcium and phosphate and a decrease in the excretion of magnesium. Supplementation with an aqueous and alcoholic extract of the leaves of Salvadora persica significantly reduced elevated urinary oxalate levels, indicating a regenerative action on endogenous oxalate synthesis. The deposition of stone-forming constituents in the kidneys of calculogenic rats was also significantly lowered by curative and preventive treatments with the aqueous and alcoholic extracts of Salvadora persica. The high serum creatinine level observed in ethylene glycol-treated rats was also reduced following treatment with the extracts. Histopathological findings showed signs of improvement after treatment with the extracts. These observations led to the conclusion that the aqueous and alcoholic extracts of the leaves of Salvadora persica are endowed with antiurolithiatic properties.     

Effects of lotus plumule supplementation before and following systemic administration of lipopolysaccharide on the splenocyte responses of BALB/c mice.

To determine whether lotus plumule supplementation alleviates acute systemic inflammation in vivo, the BALB/c mice were continuously supplemented with lotus plumule for 3 weeks, following administration with an intraperitoneal (i.p.) injection of lipopolysaccharide (LPS) at a concentration of 10mg/kg body weight (BW) to induce acute systemic inflammation. At 24h after injection of LPS, the mice were sacrificed and the visceral organ weight and splenocyte responses were measured. The results showed that lotus plumule supplementation did not significantly affect body weights and IL-6 secretion of splenocyte cultures from BALB/c mice. LPS challenge significantly increased the relative organ weights of the lungs, liver, and spleen, however low dose supplementation (40 mg/kg BW/day) with lotus plumule significantly decreased the relative organ weights of the inflammatory liver, spleen and kidney. Low dose supplementation with lotus plumule significantly increased IL-10 production of splenocyte cultures, however high dose supplementation (800 mg/kg BW/day) significantly decreased IL-10 production. These results suggest that low dose and 3-week supplementation of lotus plumule might alleviate acute systemic inflammation in vivo via decreasing the visceral organ inflammation and increasing the production of anti-inflammatory cytokine IL-10 from splenocytes. These results are valuable for developing future nutraceuticals and anti-inflammatory agents from traditional medicinal foods.     

Emerging drugs in prostate cancer

Prostate cancer is increasing in incidence more rapidly than any other malignancy. It is now the most common malignancy in men in the United States. Trends in the management of prostate cancer include earlier diagnosis and earlier intervention with surgery, radiotherapy and systemic treatments. Currently, apart from supportive care, the primary systemic treatments are endocrine therapies, in particular, LHRH agonists and anti-androgens. These agents may be used in different ways in future, particularly as adjuncts to radical local treatment which raises the prospect of improved survival. Novel therapeutic approaches such as signal transduction, anti-angiogenesis and cancer vaccines offer the best potential for the future since these are hormone-independent approaches and should therefore work across the whole range of prostate cancer. Most compounds of these kinds, however, are still early in development and are not yet proven for the management of this disease.     

Treatment of dyslipidemia in kidney transplantation

ABSTRACT

Introduction: Lipid disorders are frequent after kidney transplantation (KT) and KT recipients are considered at high- or very-high cardiovascular risk. Among many concurring factors, a major role is played by immunosuppressants.

Areas covered: General measures to manage lipid disorders first include physical activity and diet counseling. Modulating the doses of immunosuppressants also improves dyslipidemia. When lipid-lowering drugs are necessary to control elevated plasma cholesterol and/or triglycerides, statins are the cornerstone for managing hypercholesterolemia. However, side-effects (e.g. myopathy, new-onset diabetes, and kidney graft dysfunction) may occur. In these cases, ezetimibe (which does not affect kidney function) alone or on top of statins for the severe cases, is suggested by the most recent Guidelines. Proprotein convertase subtilisin/kexin type9 inhibitors are promising but expensive and their use in KT is still limited.

Expert opinion: In KT recipients, statins should be used cautiously. Rather than using high-dose statin in difficult patients, an association with ezetimibe is suggested. While fibrates, niacin, and resins do not play a relevant role due to their erratic efficacy and common side-effects, new lipid-lowering drugs are emerging but their safety and efficacy in KT patients still need to be assessed.     

Role of neural precursor cells in promoting repair following stroke

Stem cell-based therapies for the treatment of stroke have received considerable attention. Two broad approaches to stem cell-based therapies have been taken: the transplantation of exogenous stem cells, and the activation of endogenous neural stem and progenitor cells (together termed neural precursors). Studies examining the transplantation of exogenous cells have demonstrated that neural stem and progenitor cells lead to the most clinically promising results. Endogenous activation of neural precursors has also been explored based on the fact that resident precursor cells have the inherent capacity to proliferate, migrate and differentiate into mature neurons in the uninjured adult brain. Studies have revealed that these neural precursor cell behaviours can be activated following stroke, whereby neural precursors will expand in number, migrate to the infarct site and differentiate into neurons. However, this innate response is insufficient to lead to functional recovery, making it necessary to enhance the activation of endogenous precursors to promote tissue repair and functional recovery. Herein we will discuss the current state of the stem cell-based approaches with a focus on endogenous repair to treat the stroke injured brain.     

Effect of sulphated polysaccharides on erythrocyte changes due to oxidative and nitrosative stress in experimental hyperoxaluria

Kidney stones are known to haunt humanity for centuries and increase in oxalate is a predominant risk factor for stone formation. The present study was initiated with a notion to study the oxidative and nitrosative stress on erythrocytes under oxalate stress and the putative role of sulphated polysaccharides. Hyperoxaluria was induced in two groups by the administration of 0.75% ethylene glycol in drinking water for 28 days and one of them was treated with sulphated polysaccharides from Fucus vesiculosus from the 8th day to the end of the experimental period of 28 days at a dose of 5 mg/kg body weight subcutaneously. Control and drug control (sulphated polysaccharides alone) were also included in the study. Glycolic and glyoxylic acid levels of urine were analyzed as an index of hyperoxaluria. The plasma enzymic markers of cellular integrity, redox status of red blood cells, osmotic fragility, and (14)C-oxalate binding were investigated. Urine and plasma nitric oxide metabolites, expression of inducible nitric oxide synthase protein, and mRNA were assessed in kidney to evaluate the nitrosative stress. Increased levels of glycolic and glyoxylic acid in urine indicated the prevalence of hyperoxaluria in ethylene glycol-administered groups. Plasma aspartate and alanine transaminase were not altered, but alkaline phosphatase and lactate dehydrogenase of hyperoxaluric group were increased indicating tissue damage. Activities of antioxidant enzymes were decreased, whereas erythrocyte membrane lipid peroxidation was increased in hyperoxaluric rats. Moreover, an altered fragility with an increase in oxalate binding activity was observed in hyperoxaluric group. Increase in nitric oxide metabolites levels in urine and plasma along with an increase in expression of inducible nitric oxide synthase protein and mRNA in kidney were observed in hyperoxaluric rats. Administration of sulphated polysaccharides to hyperoxaluric rats averted the abnormal increase in urinary glycolic and glyoxylic acid levels and enzyme activities, decreased lipid peroxidation, and increased the activities of antioxidant enzymes. Furthermore, increased nitrosative stress accompanying hyperoxaluria was also normalized on sulphated polysaccharides treatment. To conclude, sulphated polysaccharide administration was able to maintain the integrity of erythrocyte membrane and decrease the damage to erythrocytes in hyperoxaluria.     

Administration of Antithymocyte Globulin (Rabbit) to Treat a Severe,Mixed Rejection Episode in a Pregnant Renal Transplant Recipient

Pregnancy in solid organ transplant recipients carries numerous risks to the mother such as increased risk of rejection, gestational diabetes mellitus, and preeclampsia. The developing fetus is subjected to risks such as birth defects, preterm delivery, and low birth weight. Typically, these risks can be managed through intensive, multidisciplinary prenatal care and a proper immunosuppressive regimen. In the setting of rejection, however, little data are available to suggest safe and effective treatment of acute cellular rejection, antibody‐mediated rejection, or mixed rejection episodes in the pregnant solid organ transplant recipient. We describe the first case, to our knowledge, in which antithymocyte globulin (rabbit) was used to successfully treat a pregnant renal transplant recipient who experienced a mixed rejection episode. A 22‐year‐old, African American woman with stage 6 chronic kidney disease received a deceased donor renal transplant after undergoing hemodialysis for 3 years. Her maintenance immunosuppressive regimen at the time of transplantation consisted of tacrolimus, prednisone, and mycophenolate mofetil. Despite counseling efforts on the importance of having a planned pregnancy after kidney transplantation so that her immunosuppressive medications could be optimized, the patient became pregnant 12 months later; her mycophenolate mofetil was changed to azathioprine to reduce the risk of fetal deformities or death. Three months later, the patient was admitted for biopsy of her transplanted kidney and was evaluated for possible kidney rejection. After confirmation of a mixed 1B acute cellular rejection and antibody‐mediated rejection episode, the patient decided to pursue resolution of her rejection episode and continue the pregnancy despite the potential risks to the fetus. She was treated with high‐dose corticosteroids, intravenous immunoglobulin, plasmapheresis, and antithymocyte globulin (rabbit). Twenty‐nine months after transplantation, the patient was induced and gave birth to a healthy baby boy. Our patient's case offers unique insight into the potential management of a rejection episode requiring aggressive immunosuppressive therapy. Although potent immunosuppressive therapies were successfully used in our patient, further studies are needed to make definitive recommendations regarding the use of such therapies for treatment of rejection episodes in pregnant solid organ transplant recipients. The risks and uncertainties of treating rejection episodes should always be discussed with and understood by the patient before an informed decision is made.     

活体肾移植供者肾小球滤过率与受者移植肾功能关系的研究

目的:探讨活体肾移植中供者术前肾小球滤过率(GFR)与受者移植肾功能之间的关系.方法:分析无急性排斥反应、无移植肾功能延迟恢复、随访满2年的活体肾移植患者125例,采用相关分析法分析供者术前肾小球滤过率与受者术后1周、1年、2年肾小球滤过率之间的关系.采用多元线性回归方法分析影响受者术后1年GFR的因素.结果:供者GFR与受者术后1周、1年、2年的GFR相关(r分别为0.217、0.216和0.273,P＜0.05).根据多元线性回归分析得出供者GFR和受者体质量是受者术后1年GFR重要的预测因素,线性回归方程为受者术后1年GFR=78.7-0.474×受者体质量+0.239×供者GFR.结论:活体肾移植供者术前GFR为移植肾功能的重要预测因素.     

Effect of Hygrophila spinosa in ethylene glycol induced nephrolithiasis in rats

Objective:

Hygrophila spinosa (Acanthaceae) is traditionally used to treat urinary calculi. The present study aimed to evaluate the antiurolithiatic activity of methanolic extract of Hygrophila spinosa (Acanthaceae) in ethylene glycol induced nephrolithiasic rats.

Materials and Methods:

Methanolic extract of Hygrophila spinosa (HSME) (250 and 500 mg/ kg body weight) was administered orally to male Wistar albino rats. Ethylene glycol (EG) was used to induce nephrolithiasis. The parameters studied included water intake, urinary volume, urinary pH, urinary and kidney oxalate and calcium, urinary magnesium and serum uric acid.

Results:

Ethylene glycol feeding resulted in hyperoxaluria as well as increased renal excretion of calcium and serum uric acid along with decreased excretion of urinary magnesium. Treatment with HSME significantly reduced the elevated urinary oxalate, urinary calcium and serum uric acid with increase in reduced urinary magnesium. Ethylene glycol feeding also resulted in increased levels of calcium and oxalate in kidney which was decreased after the treatment with HSME. The increased deposition of stone forming constituents in the kidneys of ethylene glycol treated rats was significantly lowered by treatment with HSME.

Conclusion:

The results indicate that the aerial parts of Hygrophila spinosa are endowed with antiurolithiatic activity, thereby justifying its traditional claim.KEY WORDS: Ethylene glycol, Hygrophila spinosa, kidney stones, nephrolithiasis