allopurinol and Nephrolithiasis

The incidence of pediatric nephrolithiasis is on the rise, with a significant related morbidity and a concomitant relevant increase in healthcare costs. The purpose of this review is to portray the current epidemiology and cause of renal stones in children, to provide a framework for appropriate clinical evaluation on an individual basis, and a guidance regarding treatment and prevention for the significant risk of lifelong recurrence and deriving complications.. The early identification of modifiable risk factors and other abnormalities is essential, to prevent related morbidity, the onset of chronic kidney disease, and the associated increased risk of developing other diseases. The implementation of risk reduction strategies, including dietary modifications and targeted pharmacological therapies, will significantly influence stone recurrences and preserve renal function.. Future research is desirable, with the aim to strengthen personalized conservative management of pediatric nephrolithiasis as first-line treatment.

Topics: Allopurinol; Chelating Agents; Child; Conservative Treatment; Diet; Diet Therapy; Diuretics; Diuretics, Potassium Sparing; Environment; Enzyme Inhibitors; Humans; Nephrolithiasis; Penicillamine; Potassium Citrate; Risk Factors; Sodium Chloride Symporter Inhibitors; Tiopronin

Nearly one-third of patients with calcium stones have hyperuricosuria. In vitro studies and clinical trials have investigated the relationship between uric acid and calcium stones, but the association between hyperuricosuria and calcium stone formation in patients is still being debated. Uric acid appears to cause salting out of calcium oxalate in human urine. However, the importance of this in vitro phenomenon to the proposed association is not supported in cross-sectional observational studies. A small placebo-controlled randomized clinical trial showed that allopurinol decreased the rate of recurrent calcium oxalate calculi in patients with hyperuricosuria and normocalciuria. An assessment of the effect of combination therapy of allopurinol with indapamide showed no additive effect. Allopurinol may have antioxidant effects that are responsible for its reducing calcium stone formation, which are independent of xanthine oxidase inhibition. In addition, a newer xanthine oxidoreductase inhibitor, febuxostat, may also be effective in the prevention of calcium stones, as it reduces urinary uric acid excretion.

Topics: Allopurinol; Biomarkers; Calcium Oxalate; Febuxostat; Humans; Indapamide; Kidney; Nephrolithiasis; Risk Factors; Treatment Outcome; Uric Acid; Uricosuric Agents

This review summarizes recent literature on advances regarding renal and ureteral calculi, with particular focus in areas of recent advances in the overall field of urolithiasis. Clinical management in everyday practice requires a complete understanding of the issues regarding metabolic evaluation and subgrouping of stone-forming patients, diagnostic procedures, effective treatment regime in acute stone colic, medical expulsive therapy, and active stone removal. In this review we focus on new perspectives in managing nephrolitihiasis and discuss recentadvances, including medical expulsive therapy, new technologies, and refinements of classical therapy such as shock wave lithotripsy, give a fundamental modification of nephrolithiasis management. Overall, this field appears to be the most promising, capable of new developments in ureterorenoscopy and percutaneous approaches. Further improvements are expected from robotic-assisted procedures, such as flexible robotics in ureterorenoscopy.

Topics: Allopurinol; Citrates; Humans; Lithotripsy; Nephrolithiasis; Robotics; Thiazides; Ureterolithiasis; Ureteroscopy; Xanthine Oxidase

Optimum management to prevent recurrent kidney stones is uncertain.. To evaluate the benefits and harms of interventions to prevent recurrent kidney stones.. MEDLINE, Cochrane, and other databases through September 2012 and reference lists of systematic reviews and randomized, controlled trials (RCTs).. 28 English-language RCTs that studied treatments to prevent recurrent kidney stones and reported stone outcomes.. One reviewer extracted data, a second checked accuracy, and 2 independently rated quality and graded strength of evidence.. In patients with 1 past calcium stone, low-strength evidence showed that increased fluid intake halved recurrent composite stone risk compared with no treatment (relative risk [RR], 0.45 [95% CI, 0.24 to 0.84]). Low-strength evidence showed that reducing soft-drink consumption decreased recurrent symptomatic stone risk (RR, 0.83 [CI, 0.71 to 0.98]). In patients with multiple past calcium stones, most of whom were receiving increased fluid intake, moderate-strength evidence showed that thiazides (RR, 0.52 [CI, 0.39 to 0.69]), citrates (RR, 0.25 [CI, 0.14 to 0.44]), and allopurinol (RR, 0.59 [CI, 0.42 to 0.84]) each further reduced composite stone recurrence risk compared with placebo or control, although the benefit from allopurinol seemed limited to patients with baseline hyperuricemia or hyperuricosuria. Other baseline biochemistry measures did not allow prediction of treatment efficacy. Low-strength evidence showed that neither citrate nor allopurinol combined with thiazide was superior to thiazide alone. There were few withdrawals among patients with increased fluid intake, many among those with other dietary interventions and more among those who received thiazide and citrate than among control patients. Reporting of adverse events was poor.. Most trial participants had idiopathic calcium stones. Nearly all studies reported a composite (including asymptomatic) stone recurrence outcome.. In patients with 1 past calcium stone, increased fluid intake reduced recurrence risk. In patients with multiple past calcium stones, addition of thiazide, citrate, or allopurinol further reduced risk.. Agency for Healthcare Research and Quality.

Topics: Adult; Allopurinol; Antimetabolites; Carbonated Beverages; Citrates; Drinking; Enzyme Inhibitors; Fluid Therapy; Humans; Hydroxamic Acids; Nephrolithiasis; Practice Guidelines as Topic; Secondary Prevention; Thiazides; Treatment Outcome

Kidney stone disease remains a major health and economic burden on the nation. It has been increasingly recognized that nephrolithiasis can be both a chronic or systemic illness. There have been major limitations in the development of new drugs for the prevention and management of this disease, largely due to our lack of understanding of the complex pathophysiologic mechanisms involving the interaction of three major target organs: the kidney, bone, and intestine. We also do not yet understand the molecular genetic basis of this polygenic disorder. These limitations are coupled with the incorrect perception that kidney stone disease is solely an acute illness, and the lack of reliable tests to assess outcome measures. All of these factors combined have diminished the willingness of the pharmaceutical industry to engage in the development of novel drugs.

Topics: Alkalies; Allopurinol; Animals; Drug Design; Enzyme Inhibitors; Humans; Nephrolithiasis; Sodium Chloride Symporter Inhibitors

To evaluate, by means of a prospective randomized study, the efficacy of cinacalcet in the forms of nephrolithiasis associated with primary hyperparathyroidism in both the hypercalcemic and normocalcemic variant.. Ten patients suffering from active nephrolithiasis associated with primary hyperparathyroidism (4 hypercalcemics and 6 normocalcemics), equally divided between males and females, were randomly but not blindly addressed to treatment with potassium citrate and allopurinol, or to the same therapeutic regimen in combination with cinacalcet. The dosage of cinacalcet was optimized for each patient in order to obtain a reduction of parathyroid hormone (PTH) within normal limits while enabling the maintenance of adequate calcemic values. All study participants were given the same diet based on a reduction in sodium intake, oxalate-rich foods and animal protein with standardized intake of calcium and an increase in hydration. After a follow up period of 10 months , cinacalcet was associated to standard therapy and diet in patients who were not taken it, conversely cinacalcet was withdrawn in the remaining patients who remained on standard therapeutic regimen and diet. Follow up was continued for a second period of observation of the same duration of the first.. At the end of the period of treatment with cinacalcet, for both variants of hyperparathyroidism, a statistically significant reduction in the overall number and in the diameter of renal stones was found.. This prospective randomized study shows the effectiveness of cinacalcet used in combination with a diet with normalized calcium intake, in reducing the number and size of urinary stones in hypercalemic and normocalcemic forms of primary hyperparathyroidism.

Topics: Aged; Allopurinol; Calcimimetic Agents; Cinacalcet; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Hypercalcemia; Hyperparathyroidism, Primary; Male; Middle Aged; Naphthalenes; Nephrolithiasis; Pilot Projects; Potassium Citrate; Prospective Studies; Treatment Outcome

Tumor lysis syndrome (TLS) is a metabolic disorder caused by massive tumor lysis. Hypouricemic agents are administered to prevent TLS-related hyperuricemia and renal failure. We experienced three cases of urine xanthine crystals during TLS in patients with hematologic malignancies who received prophylactic febuxostat. Yellowish and pinkish deposits were observed in urinary tract catheters and urinary bags. Urine microscopy revealed that the deposits were xanthine crystals. In rapid tumor lysis, inhibition of xanthine oxidase can cause xanthine accumulation and urine xanthine crystallization. During TLS, urine xanthine crystals may be overlooked, so careful observation and management are required to avoid xanthine nephropathy.

Topics: Allopurinol; Hematologic Neoplasms; Humans; Microscopy; Neoplasms; Nephrolithiasis; Tumor Lysis Syndrome; Urinalysis; Xanthine

Present research study was conducted to formulate kidney-targeted allopurinol (AO)-loaded chitosan nanoparticles (ANPs) for management of hyperuricemic related nephrolithiasis. Different molecular weights of chitosan were used for fabricating ANP formulation by adopting modified ionotropic gelation method. The prepared batches were than evaluated for particle size analysis, entrapment efficiency, transmission electron microscopy, X-ray diffraction, Differential Scanning Calorimetry, in vitro release and in vivo animal study. The in vivo study depicted that post 2 h of administration of different formulations and pure drug; ANPs prepared from low molecular weight chitosan showed maximum concentration of AO in kidney signifying successful kidney targeting of drug (25.92 fold) whereas no or very less amount of AO was seen in other animal groups. Effectiveness (p < 0.01) of formulation in management of hyperuricemia-associated nephrolithiasis was also evaluated via estimation of urine pH and serum and urine uric acid levels of mice. Further histological study was also performed on kidney samples which again affirmed these results. Present investigation demonstrated that ANPs prepared from low MW chitosan depicted maximum kidney-targeting ability that might be due to its specific uptake by the kidneys as well as its higher solubility than other two polymers, which results in enhanced release rate from the formulation and also offers an efficient strategy for the management of hyperuricemic nephrolithiasis.

Topics: Allopurinol; Animals; Chitosan; Drug Carriers; Female; Humans; Hyperuricemia; Kidney; Male; Mice; Molecular Weight; Nanoparticles; Nephrolithiasis; Particle Size

This study aimed to investigate the efficacy and safety of febuxostat in patients with radiolucent nephrolithiasis.. From March 2016 to June 2018, data of 96 patients with radiolucent nephrolithiasis and hyperuricemia who referred to the Third Affiliated Hospital of Sun Yat-sen University were retrospectively analyzed. These patients were divided into allopurinol 300mg/d (control), febuxostat 40mg/d (F40) and 80mg/d (F80) groups respectively. All patients took potassium citrate as a combination treatment and had been followed up for at least 6 months. Before treatment and on after 1st, 3rd and 6th month, complete blood count, serum uric acid (sUA), hepatic and renal function as well as ultrasound were carried out. Arthritic and gastrointestinal symptoms were also monitored. Computed tomography was performed before treatment and 6 months after medication.. Compared with allopurinol group, F40 group showed no difference in urate-lowering effect, while F80 had the best effect across all the visits (P<0.01). At 6th month, 25(83.3%) cases of F80 group achieved sUA<6mg/ dL, which was better than allopurinol group (18 cases, 58.1%) and F40 group (17 cases, 58.6%). In the dissolution effect of radiolucent calculi, F80 had the best effect, followed by F40 and then allopurinol (P<0.05). No statistical difference was observed in adverse events among three groups.. Febuxostat significantly decreased sUA, promoted radiolucent stone dissolution and reduced the total stone number, whereas it did not increase the adverse events.

Topics: Adult; Aged; Allopurinol; Febuxostat; Female; Humans; Hyperuricemia; Male; Middle Aged; Nephrolithiasis; Retrospective Studies; Young Adult

The aim of present research work was to design, fabricate, optimize, and evaluate allopurinol (ALLO)-loaded bovine serum albumin nanoparticles (ABNPs) for kidney targeting of the drug and exploring the potential of fabricated ABNPs for management of hyperuricemia-related nephrolithiasis. ABNP formulation was prepared by employing desolvation technique, and its optimization was conducted by 2-factor-3-level central composite design (CCD) in order to achieve minimum particle size (PSA) and polydispersity index (PDI), maximum entrapment efficiency (EE), and zeta potential (ZP). Further, the optimized formulation (ABNPs

Topics: Allopurinol; Animals; Drug Carriers; Drug Compounding; Gout Suppressants; Humans; Hyperuricemia; Kidney; Mice; Nanoparticles; Nephrolithiasis; Particle Size; Serum Albumin, Bovine

The major short coming of conventional therapy system is that they can't deliver the therapeutics specifically to a site within the body without producing nonspecific toxicity. Present research aimed at developing kidney targeted allopurinol (AP) loaded chitosan coated magnetic nanoparticles (A-MNPs) for the management of hyperuricemic nephropathy manifested in the form of nephrolithiasis.. The work includes preparation of magnetic nanoparticles by chemical co-precipitation method and evaluation of the prepared batches for particle size analysis, Transmission electron microscopy, entrapment efficiency, in-vitro release study etc. Further, FTIR spectroscopy, X-ray diffraction, Differential Scanning Calorimetry, Vibrational sample magnetometer (VSM) and in-vivo animal studies were also performed.. VSM analysis demonstrates that the prepared nanoparticles exhibit superparamagnetic magnetic behaviour which was retained even after coating by chitosan. In-vivo studies of A-MNPs showed 19.07-fold increase in kidney uptake of AP as compared to serum post 2 h of administration in mice whereas no drug was detected in kidney and serum post 2 h administration of pure drug (free-form) indicating successful targeting to kidney as well as sustained release of AP from the formulated A-MNPs. The significant (p < 0.01) effectiveness of A-MNPs in management of hyperuricemic nephrolithiasis was observed through estimating pH and uric acid levels in urine and serum samples of mice. These findings were also confirmed by histological examination of isolated kidney samples.. Present investigation signifies that a simple external magnetic field is enough for targeting allopurinol to kidneys by formulating A-MNPs which further offers an effective approach for management of hyperuricemic nephrolithiasis. Graphical Abstract.

Topics: Administration, Oral; Allopurinol; Animals; Chemical Precipitation; Chitosan; Disease Models, Animal; Drug Delivery Systems; Kidney; Magnetite Nanoparticles; Mice; Nanoparticles; Nephrolithiasis; Oxonic Acid; Uric Acid

Uric acid (UA) nephrolithiasis represents 10% of kidney stones in the US with low urine pH and high saturation of UA as the main risk factors for stone development. Dissolution therapy for UA kidney stones via urinary alkalization has been described as a treatment option. We present our experience in treating UA nephrolithiasis with medical dissolution therapy.. A retrospective review was performed of UA stone patients referred for surgery but treated with dissolution therapy between July 2007 and July 2016. Patients were identified using ICD-9 codes. Patients were treated with potassium citrate alone or in combination with allopurinol. Serial imaging and urine pH were obtained at follow-up. Demographics, aggregate stone size, time to stone clearance, urine pH (office dip), and complications were recorded.. Twenty-four patients (14 men and 10 women) were identified that started medical dissolution therapy for UA nephrolithiasis after initial referral for surgical management. Three patients (13%) did not tolerate the initiation of dissolution therapy and discontinued this treatment. Of the 21 patients that were maintained on dissolution therapy, 14 patients (67%) showed complete resolution of nephrolithiasis and 7 patients (33%) showed partial reduction. Patients with partial response had a mean reduction in stone burden of 68%. There were 3 recorded complications (UTI, GI upset with therapy, and throat irritation) and 4 recorded stone recurrences among these 21 patients.. Based on our study population, medical dissolution therapy is a well-tolerated, non-invasive option for UA nephrolithiasis.

Topics: Adult; Aged; Allopurinol; Female; Humans; Kidney Calculi; Male; Middle Aged; Nephrolithiasis; Potassium Citrate; Retrospective Studies; Uric Acid

The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on the comparative effectiveness and safety of preventive dietary and pharmacologic management of recurrent nephrolithiasis in adults.. This guideline is based on published literature on this topic that was identified using MEDLINE, the Cochrane Database of Systematic Reviews (through March 2014), Google Scholar, ClinicalTrials.gov, and Web of Science. Searches were limited to English-language publications. The clinical outcomes evaluated for this guideline include symptomatic stone recurrence, pain, urinary tract obstruction with acute renal impairment, infection, procedure-related illness, emergency department visits, hospitalizations, quality of life, and end-stage renal disease. This guideline grades the quality of evidence and strength of recommendations using ACP's clinical practice guidelines grading system. The target audience for this guideline is all clinicians, and the target patient population is all adults with recurrent nephrolithiasis (≥1 prior kidney stone episode).. ACP recommends management with increased fluid intake spread throughout the day to achieve at least 2 L of urine per day to prevent recurrent nephrolithiasis. (Grade: weak recommendation, low-quality evidence).. ACP recommends pharmacologic monotherapy with a thiazide diuretic, citrate, or allopurinol to prevent recurrent nephrolithiasis in patients with active disease in which increased fluid intake fails to reduce the formation of stones. (Grade: weak recommendation, moderate-quality evidence).

Topics: Adult; Allopurinol; Calcium Chelating Agents; Citric Acid; Fluid Therapy; Gout Suppressants; Humans; Nephrolithiasis; Secondary Prevention; Sodium Chloride Symporter Inhibitors

A 30-year-old man was referred for investigation and management of hyperuricaemia. History included recurrent nephrolithiasis and chronic gout with poor response to medical management. Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) enzyme activity was investigated and found to be deficient confirming the diagnosis of Lesch-Nyhan disease. Hyperuricaemia was treated with allopurinol. To prevent nephrolithiasis, the patient was instructed to avoid dehydration and aim for a minimum urine output of 2 L/day. Urinary alkalinisation with potassium citrate was started. The patient was referred for genetic counselling. This case discusses the genetics, pathophysiology, clinical manifestations, diagnosis and management of HGPRT deficiency.

Topics: Adult; Allopurinol; Diuretics; Genetic Counseling; Gout; Gout Suppressants; Humans; Hyperuricemia; Hypoxanthine Phosphoribosyltransferase; Lesch-Nyhan Syndrome; Male; Nephrolithiasis; Potassium Citrate; Uric Acid

Tumor lysis syndrome is a potentially life-threatening complication of induction chemotherapy for treatment of lymphoproliferative malignancies. Serious complications of tumor lysis syndrome are rare with the preemptive use of allopurinol, rasburicase, and urine alkalinization. We report a case of oliguric acute renal failure due to bilateral xanthine nephropathy in an 11-year-old girl as a complication of tumor lysis syndrome during the treatment of T-cell acute lymphoblastic leukemia. Xanthine nephrolithiasis results from the inhibition of uric acid synthesis via allopurinol which increases plasma and urinary xanthine and hypoxanthine levels. Reports of xanthine nephrolithiasis as a cause of tumor lysis syndrome are rare in the absence of defects in the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) enzyme. Xanthine nephropathy should be considered in patients who develop acute renal failure following aggressive chemotherapy with appropriate tumor lysis syndrome prophylaxis. Urine measurements for xanthine could aid in the diagnosis of patients with nephrolithiasis complicating tumor lysis syndrome. Allopurinal dosage should be reduced or discontinued if xanthine nephropathy is suspected.

Topics: Acute Kidney Injury; Allopurinol; Child; Enzyme Inhibitors; Female; Humans; Nephrolithiasis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Tumor Lysis Syndrome; Xanthine

Percutaneous nephrolithotomy is a commonly used procedure for treatment of large or complex renal calculi. In some instances postoperative residual stone fragments are an unavoidable result. Yet to our knowledge no study has examined the impact of medical management on stone formation in patients with or without residual fragments following percutaneous nephrolithotomy. Thus, we have conducted the first investigation of aggressive medical management following percutaneous nephrolithotomy and its impact on stone formation rates in patients with and without residual fragments.. A total of 70 patients who underwent percutaneous nephrolithotomy and received counseling regarding selective medical management following a comprehensive metabolic evaluation, were identified. Patients were placed into 4 groups following percutaneous nephrolithotomy, that is stone-free or residual fragments, who underwent or did not undergo medical therapy. New stone formation was assessed by spontaneous stone passage in the absence of residual stone fragments, stone passage without change in the number of residual fragments, surgical removal of newly formed stones, or appearance of new stones or increase in size of stone or fragments on abdominal radiographs. Stone remission rates were also calculated.. Selective medical therapy significantly decreased stone formation rates in the stone-free (0.67 stones per patient per year vs 0.02) and residual fragment groups (0.67 stones per patient per year vs 0.02) as determined by the Wilcoxon signed rank test (p<0.0001). Moreover, remission was observed in a higher proportion of patients in the medically treated stone-free and residual fragment groups (87% and 77%) when compared to the same groups without medical therapy (29% and 21%, chi-square test p<0.0001).. Our findings suggest that comprehensive metabolic evaluation and aggressive medical management can control active stone formation and growth in patients with or without residual stone fragments after percutaneous nephrolithotomy. Given the inherent morbidity and increased costs attendant with repeat procedures, medical management should be instituted in patients following percutaneous nephrolithotomy without regard to stone-free status.

Topics: Allopurinol; Diuretics; Drug Therapy, Combination; Female; Follow-Up Studies; Gout Suppressants; Humans; Male; Nephrolithiasis; Nephrostomy, Percutaneous; Potassium Citrate; Radiography, Abdominal; Retrospective Studies; Secondary Prevention; Sodium Chloride Symporter Inhibitors; Time Factors; Treatment Outcome