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PubMed2002

Spindle and cuboidal renal cell carcinoma, a tumour having frequent association with nephrolithiasis: report of 11 cases including a case with hybrid conventional renal cell carcinoma/ spindle and cuboidal renal cell carcinoma components.

AIMS: We present the largest series of an unclassified subtype of renal cell carcinoma, which seems to be a distinct morphological entity and which is sometimes designated as spindle and cuboidal renal cell carcinoma. METHODS AND RESULTS: Eleven cases of spindle and cuboidal renal cell carcinoma were found among 7000 primary renal cell tumours in Pilsen's routine and consultation files. The patients were five men and six women. They ranged in age from 22 to 65 years (mean 56.8). Microscopically, the tumours were composed of two main populations of cells. First, the preponderant type of cells was formed by flattened, spindle cells with sparse cytoplasm. The second cell type was a small cuboidal cell with clear to light eosinophilic cytoplasm. Spindle-shaped cells were arranged in a fascicular pattern often reminiscent of low-grade smooth muscle tumours. Solid areas of spindle cells were also present. Small cuboidal cells formed sparse tubular structures lined by a row of single cells. In addition to all previous published cases of spindle and cuboidal renal cell carcinoma we observed an association of nephrolithiasis in our cases. It was seen in 3/11 of our patients. A previously unreported feature is the occurrence of a conventional renal cell carcinoma component in one of our cases. Seven of our patients are currently well without signs of recurrence or metastasis, one had metastasis in a regional lymph node at the time of nephrectomy, one died of an unrelated condition, and two were lost to follow-up. CONCLUSIONS: We present 11 cases of spindle and cuboidal renal cell carcinoma, which is believed to be a distinctive morphological entity. Our cases were histologically, immunohistochemically and ultrastructurally similar to the previously reported cases of spindle and cuboidal renal cell carcinoma. In contrast to all previously reported cases of spindle and cuboidal renal cell carcinoma, we observed an association with nephrolithiasis in three of our cases; moreover, one of our tumours had a conventional renal cell carcinoma component and another revealed a metastatic focus in a regional lymph node. None of our patients died of the disease. This study confirms that spindle and cuboidal renal cell carcinoma has a low malignant potential.

Adult↗

PubMed1998

The incidence of lower-pole nephrolithiasis--increasing or not?

OBJECTIVE: To determine if the incidence of lower-pole nephrolithiasis is increasing. METHODS: A previously published meta-analysis of trends in the location of stones in the kidney, using data from 1984 to 1992, determined the percentage of lower pole stones in 26,722 kidney stones treated by extracorporeal shockwave lithotripsy (ESWL). We performed prospective studies on all patients treated by ESWL for a single renal stone (not manipulated from the ureter) in two organizations: at Lithotripters Inc., 47,303 stones were treated with ESWL by 1000 urologists in private practice from 1989 to 1995. At the Midwest Urologic Stone Unit, 9357 stones were treated with ESWL by 200 urologists in private practice from 1987 to 1995. The distribution of stones in both samples was compared with that reported earlier. RESULTS: The meta-analysis for stone location trends from the previously published article suggested that the percentage of kidney stones in the lower pole at ESWL increased erratically from 1984 to 1989 but was then stable for 3 years. The Lithotripters Inc. sample showed an essentially constant incidence from 28% in 1990 to 30% in 1995, and the Midwest Urologic Stone Unit sample showed an essentially constant incidence from 35% in 1988 to 36% in 1995. CONCLUSION: The incidence of lower pole nephrolithiasis has remained stable from 1990.

Humans↗

PubMed2000

Possible biphasic changes of free radicals in ethylene glycol-induced nephrolithiasis in rats.

OBJECTIVE: To evaluate the possible role of free radicals in nephrolithiasis in rats induced by ethylene glycol, and to examine the correlation between the urinary enzymes N-acetyl-beta-glucosaminidase (NAG), beta-galactosidase (GAL) and neutral endopeptidase (NEP), and free radical production. MATERIALS AND METHODS: Hyperoxaluria was produced in male Wistar rats by adding ethylene glycol to their drinking water. After 7, 21 and 42 days of treatment, urinary oxalate, creatinine clearance and urinary enzymes (NAG, GAL and NEP) were measured. The nitroblue tetrazolium perfusion method was used to locate the sites of free-radical production. Ultrasensitive chemiluminescence was used to directly measure the production of reactive oxygen species (ROS) in vivo. Vitamin E and potassium citrate were fed to rats, in addition to ethylene glycol, to assess their effects on free radical production. RESULTS: Urinary oxalate increased significantly and was associated with an increase in NAG and GAL at all sample times. However, urinary NEP activity was unchanged on day 7, although there was four times as much NEP on days 21 and 42 than in the control groups. Formazan particles in the renal cortex were scored as 3+ to 4+ in rats treated for 7 days with ethylene glycol. Blood ROS levels were also higher in this group than in the controls (P < 0.01). After vitamin E and potassium citrate treatment, blood ROS levels were lower than in rats treated with ethylene glycol alone. CONCLUSION: Free radicals may be produced in the early stages of nephrolithiasis in rats fed with ethylene glycol. Free radicals occurred mainly in blood and might be associated with NEP inactivation.

Animals↗

PubMed2003

Urine stone risk factors in nephrolithiasis patients with and without bowel disease.

BACKGROUND: The prevalence of nephrolithiasis among patients with bowel disease is higher than in the general population. We examined urine stone risk factors and clinical characteristics of these patients, contrasted with a large group of stone forming patients without systemic disease. METHODS: A total of 180 patients with bowel disease were compared with a group of 2048 nephrolithiasis patients with calcium or uric acid stones and without systemic diseases. Bowel diseases included inflammatory bowel disease with and without bowel resections, bowel resections from cancer or trauma, and bypass procedures for obesity or hypercholesterolemia. Urine stone risk factors, stone rates, stone compositions, and creatinine clearance were measured. RESULTS: Compared to ordinary stone forming patients, bowel patients formed stones higher in rate of recurrence and in uric acid content. Uric acid content was highest when colon surgery had occurred. Urine volumes were low among all bowel patients except those with a bypass. Average creatinine clearance values were low among all bowel patients. Urine oxalate excretion was modestly elevated after small bowel resection, but very high with bypass. Supersaturations were increased mainly by low urine volume and-for uric acid-low pH. Patients with no surgery were indistinguishable from routine stone formers. CONCLUSIONS: Low urine volume and pH are the main stone-forming abnormalities in bowel disease patients. Hyperoxaluria is extreme after bypass, but only modest after small bowel surgery. In the absence of surgery, bowel disease patients with stones cannot be distinguished from common stone formers by comprehensive stone risk measurements.

Calcium Oxalate↗

PubMed2004

Genetics of hypercalciuria and calcium nephrolithiasis: from the rare monogenic to the common polygenic forms.

Idiopathic calcium nephrolithiasis is a multifactorial disease with a pathogenesis that involves a complex interaction of environmental and individual factors. This review discusses what is known about monogenic renal calcium stone-related disorders, provides an update on genetic research in calcium nephrolithiasis and such intermediate phenotypes as idiopathic hypercalciuria, discusses the problems that these conditions pose to clinicians and geneticists interested in their pathogenesis, and proposes some method tools potentially useful in this research frame of reference.

Animals↗

PubMed1978

Effect of parathyroid extract on renal cyclic AMP excretion in patients with normocalciuric nephrolithiasis.

It is uncertain whether normocalcemic, normocalciuric patients with calcium nephrolithiasis have a disorder of calcium metabolism. We studied the effect of a parathyroid extract (PTE) INFUSION (1.4 U/kg body weight) on the urinary cyclic AMP excretion in 16 such patients. For comparison, we investigated groups of normal individuals and patients with primary hyperparathyroidism, renal insufficiency and different gastrointestinal diseases. The increase of cyclic AMP above basal excretion in patients with nephrolithiasis was only 1.2 +/- 0.3 mumol/h (mean +/- SEM), versus 2.5 +/- 0.5 mumol/h in normal subjects (p less than 0.05) although the basal excretion was similar. Patients with renal insufficiency had low basal excretion of cyclic AMP and little stimulation of excretion by PTH (increase, 0.3 +/- 0.06 mumol). Patients with primary hyperparathyroidism had high baseline cyclic AMP excretion but sub-normal stimulation by PTE (increase, 0.46 +/- 0.13); in contrast, patients with different gastrointestinal disease had high baseline excretion and supranormal stimulation of cyclic AMP excretion (increase, 5.2 +/- 0.6). We speculate that an impaired response to PTH might be involved in the slightly increased urinary calcium excretion in normocalcemic stone formers suggested by others.

Adolescent↗

PubMed2003

Carcinosarcoma and squamous cell carcinoma of the renal pelvis associated with nephrolithiasis: a case report of each tumor type.

Both squamous cell carcinoma and carcinosarcoma of the renal pelvis are uncommon. We report on two cases, one carcinosarcoma and one squamous cell carcinoma of the renal pelvis. In the patient with squamous cell carcinoma of the left kidney, the tumor was neither detectable on preoperative radiological evaluation nor grossly visible in the surgical specimen. This patient, a 56-year-old man, presented with left lumbar pain, hematuria, fever, 4-5 kg weight loss, and untreated nephrolithiasis of the left kidney that had been diagnosed 20 years earlier. The second patient, an 87-year-old woman, also had a long history of left kidney nephrolithiasis and presented with left lumbar pain and hematuria. Both patients underwent nephrectomy for removal of the non-functioning hydronephrotic left kidney. In both cases, microscopic examination of the surgical specimen revealed squamous metaplasia and dysplasia in the pelvicalyceal mucosa, and islands of atypical squamous cells in the renal parenchyma. In the second case, the kidney also showed sarcomatous changes in the pelvis.

Aged↗

PubMed1998

Pathogenesis of idiopathic calcium nephrolithiasis: update 1997.

Idiopathic calcium nephrolithiasis (ICN) is a frequent disease in Western countries. The physicochemical theory of lithogenesis, which explains stone formation by the precipitation, growth, and crystalline aggregation of lithogenic salts in the urine, has contributed greatly to the understanding of the pathogenesis of calcium urolithiasis. However, several aspects are still unexplained; the co-existence of familial occurrence, primary tubular dysfunctions with ICN, and anomalies in the systemic handling of oxalate and calcium led to the development of a cellular hypothesis of ICN. A number of cellular defects in the handling of ions has been reported that involves both anion and cation transport. These anomalies are probably the expression of a still unknown cellular defect in idiopathic calcium stone formers. We suggested that an anomaly in the cell membrane composition might be responsible for the complex array of cell ion flux abnormalities observed in ICN. Recently, a disorder in the n-6 polyunsaturated fatty acid series has been described; it is characterized by a lower linoleic acid content and a higher arachidonic acid concentration in both plasma and erythrocyte membrane phospholipids of renal calcium stone patients. This anomaly could cause an increased activity of ion carriers; furthermore, it may lead to increased prostaglandin synthesis and to secondary phenomena at the kidney, skeletal, and intestinal level. As a consequence, critical conditions for lithogenesis in the kidney may ensue. The data suggest a common pathogenesis for hypercalciuria and hyperoxaluria. The systemic defect in the phospholipid arachidonic acid level may be both of dietary or genetic origin; experimental data suggest that the increase in delta-6 desaturase activity, the limiting enzyme in the metabolic pathway of polyunsaturated fatty acids, might be relevant to the pathogenesis of lipid abnormalities observed in nephrolithiasis and to the pathogenesis of ICN and its related problems (at the kidney, intestinal, and bone level).

Calcium↗

PubMed2002

Topiramate-induced nephrolithiasis.

Topiramate is a recently developed antiepileptic medication that is becoming more widely prescribed because of its efficacy in treating refractory seizures. Urologists should be aware that this medication can cause metabolic acidosis in patients secondary to inhibition of carbonic anhydrase. In addition, a distal tubular acidification defect may result, thus impairing the normal compensatory drop in urine pH. These factors can lead to the development of calcium phosphate nephrolithiasis. We report the first two cases of topiramate-induced nephrolithiasis in the urologic literature.

Acids↗

PubMed2003

Nephrolithiasis associated with renal insufficiency: factors predicting outcome.

BACKGROUND AND PURPOSE: Renal calculous disease may be associated with various degrees of renal insufficiency secondary to a combination of obstruction, urinary infection, frequent surgical intervention, and coexisting medical disease. Herein, we present our data on the progression of renal function in patients with stones associated with renal insufficiency and assess the significance of various factors that could predict postoperative renal function deterioration. PATIENTS AND METHODS: Data were obtained from 4400 patients undergoing treatment for calculous disease at our institute since 1991. Renal insufficiency, defined as a baseline serum creatinine >1.5 mg/dL, was present in 84 (1.9%). Predictive factors evaluated for renal function deterioration were preoperative (age, duration of symptomatology and nephrolithiasis, urinary tract infection, coexistent medical diseases, baseline serum creatinine, and stone burden), intraoperative (number of percutaneous tracts), and postoperative (recurrent infection, proteinuria, cortical atrophy, residual fragments, and stone recurrence). RESULTS: Over a mean follow-up of 2.2 years (range 6 months-6 years), 33 patients (39.3%) showed improvement, 24 (28.6%) showed stabilization, and 27 (32.1%) showed deterioration in their renal function. Higher baseline serum creatinine, proteinuria >300 mg/day, renal cortical atrophy, stone burden >1500 mm(2), recurrent urinary infection, and age <15 years were significant predictors of subsequent renal function deterioration. CONCLUSIONS: Patients with nephrolithiasis and mild to moderate renal insufficiency warrant aggressive treatment aimed at complete stone clearance and prevention of recurrence of stones and urinary infection. A higher baseline preoperative serum creatinine, proteinuria >300 mg/day on follow-up, renal cortical atrophy, stone burden >1500 mm(2), recurrent urinary infection, and age <15 years are associated with a significantly higher likelihood of renal function deterioration after treatment of the calculous disease.

Adult↗

PubMed1997

Retrograde percutaneous nephrolithotomy using the Lawson technique for management of complex nephrolithiasis.

Percutaneous nephrolithotomy remains an important technique for managing complicated nephrolithiasis. Retrograde percutaneous nephrostomy creation has been promoted as an alternative to the standard antegrade technique. We reviewed our first 41 consecutive attempts utilizing the Lawson technique for managing patients with complicated nephrolithiasis. Percutaneous access was achieved in 40 attempts (98%). Thirty-six (90%) of the retrograde nephrostomy tracts were adequate for lithotripsy or stone extraction during the same anesthetic. Twenty-three (56%) of the kidneys treated with the Lawson procedure were rendered stone free. Nine patients had minimal residual stone burden (fewer than five fragments, 4 mm or smaller) by the time of discharge. A single Lawson procedure rendered 10 kidneys (24%) stone free. An additional 20 clinic procedures and 17 anesthetic procedures were performed on the 40 kidneys. Complications were minimal, with three patients (8%) requiring transfusion.

Adult↗

PubMed1997

Metabolic evaluation of patients with recurrent idiopathic calcium nephrolithiasis.

BACKGROUND: Metabolic evaluation in recurrent idiopathic calcium renal stone-formers (RCSF) was analysed with respect to the following questions: (1) do three 24-h urines provide more diagnostic accuracy in the metabolic evaluation of RCSF than 1 or 2 urines?; (2) does time after stone event influence the diagnostic yield?; (3) is urine composition at weekends different from that at mid-week?; (4) what are the prevalences of the most important risk factors (RF) of idiopathic calcium nephrolithiasis, i.e. low volume (LV), hypercalciuria (HC), hyperoxaluria (HO), hyperuricosuria (HU), hypocitraturia (Hypo-Cit), and hypomagnesiuria (Hypo-Mg)?; and (5) do male RCSF differ from females with respect to urinary RFs? METHODS: Seventy-five RCSF (59 men, 16 women) collected three 24-h urines (U1-3) while on free-choice diet. To account for possible variations in lifestyle and diet, U1 and U3 had to be collected midweek and U2 at a weekend. RESULTS: When considering all three urines together (U1 + U2 + U3), the number of RF abnormalities/patient was 2.8 +/- 0.1, higher than numbers of any combination of two urines or of any single urine (P = 0.0001 for all comparisons). The number of RF abnormalities also rose with time after stone event, from 0.8 +/- 0.1 (range 0-4) in U1 to 1.1 +/- 0.1 (range 0-4) in U3 (P = 0.011 vs U1). Whereas all other RF did not change between collections, urine volume was lower in U2 (1793 +/- 90 ml) than in U1 (2071 +/- 97 ml, P = 0.0001 vs U2) and U3 (1946 +/- 97 ml, P = 0.046 vs U2). At least 1 abnormality was found in 85.3% of all RCSF, and multiple abnormalities occurred in 47%. The most frequent RF was HC (39%), followed by HO and LV (32% each), Hypo-Cit (29%), HU (23%) and Hypo-Mg (19%). Males more often had Hypo-Cit (P < 0.001) and Hypo-Mg (P < 0.01) than females, whereas HO was more frequent in female RCSF (P < 0.025 vs males). CONCLUSIONS: Diagnostic accuracy of metabolic evaluation in RCSF increases both with the number of urines collected and the time passing after a stone event. Urines collected at weekends differ from those of the week only by their lower volumes. Abnormalities of RF for calcium nephrolithiasis can be detected in 85.3% of RCSF, and HC is the most common RF both in male and female RCSF.

Adult↗

PubMed1992

Pseudotuberculous pyelonephritis associated with nephrolithiasis.

This report describes a 40-year-old man with an unusual form of granulomatous pyelonephritis, associated with nephrolithiasis, resulting in end-stage kidney disease and right pretransplant nephrectomy. The kidney specimen contained a staghorn calculus and showed chronic inflammation with confluent caseating granulomas and multinucleated giant cells, resembling renal tuberculosis. However, neither tubercle bacilli nor other microorganisms were demonstrated in the renal tissue or in urine cultures. Because these findings do not support a tuberculous etiology of the granulomatous pyelonephritis, we conclude that this patient had a pseudotuberculous reaction as a consequence of nephrolithiasis.

Adult↗

PubMed1998

Variation in incidence of indinavir-associated nephrolithiasis among HIV-positive patients.

BACKGROUND: Nephrolithiasis may be an important consequence of indinavir therapy; however little has been published on the variation in incidence between different populations of patients or the possible mechanisms of calculus formation. OBJECTIVE: To examine variation in the incidence of indinavir-associated nephrolithiasis (IAN) in HIV-positive patients in relation to hemophilia and hepatitis C virus (HCV) infection. METHODS: Clinical data were abstracted retrospectively from the medical records of all adult patients treated with indinavir from September 1995 to September 1997. Occurrence of first IAN, defined as flank pain and hematuria after initiation of therapy, was analyzed in relation to hemophilia status and HCV infection. RESULTS: There were 17 episodes of IAN (22%) among 79 patients treated with indinavir. Of 10 patients with hemophilia, 50% developed IAN as compared with 17% of patients without hemophilia (P = 0.03). Median days to first IAN was 22 (range 7-110 days) for hemophiliacs and 156 (range 5-611 days) for those without hemophilia. Data for HCV status were available for 74 out of 79 patients: 10 out of 27 (37%) patients with HCV developed IAN compared with six out of 42 (14%) without HCV (P = 0.02). CONCLUSION: Overall incidence of IAN was higher than that previously reported and was significantly greater in hemophiliacs than in non-hemophiliacs. HCV may be a contributing factor.

Adult↗

PubMed1985

Nephrolithiasis in childhood inflammatory bowel disease.

Six children with inflammatory bowel disease and nephrolithiasis are reported. Their mean age at the passage of the first stone was 12.5 years and the mean duration of active inflammatory bowel disease was 34.5 months. Four had ulcerative colitis and two had Crohn's disease. In three patients, the onset of stone disease was associated with a flare in the bowel disease. Stone passage in four patients was accompanied by an increase in abdominal pain; three experienced gross hematuria. Stones from four of the patients were composed primarily of calcium phosphate; stones from the remaining patients contained uric acid and/or calcium oxalate. The pathogenesis of nephrolithiasis as it relates to inflammatory bowel disease is considered and an approach to therapy offered.

Adolescent↗

PubMed2004

Novel insights into the pathogenesis of uric acid nephrolithiasis.

PURPOSE OF REVIEW: The factors involved in the pathogenesis of uric acid nephrolithiasis are well known. A low urinary pH is the most significant element in the generation of stones, with hyperuricosuria being a less common finding. The underlying mechanism(s) responsible for these disturbances remain poorly characterized. This review summarizes previous knowledge and highlights some recent developments in the pathophysiology of low urine pH and hyperuricosuria. RECENT FINDINGS: Epidemiological and metabolic studies have indicated an association between uric acid nephrolithiasis and insulin resistance. Some potential mechanisms include impaired ammoniagenesis caused by resistance to insulin action in the renal proximal tubule, or substrate competition by free fatty acids. The evaluation of a large Sicilian kindred recently revealed a putative genetic locus linked to uric acid stone disease. The identification of novel complementary DNA has provided an interesting insight into the renal handling of uric acid, including one genetic cause of renal uric acid wasting. SUMMARY: The recognition of metabolic, molecular, and genetic factors that influence urinary pH, and uric acid metabolism and excretion, will provide novel insights into the pathogenesis of uric acid stones, and open the way for new therapeutic strategies.

Circadian Rhythm↗

PubMed1990

Antacid-induced phosphate depletion syndrome presenting as nephrolithiasis.

A 29-year-old insulin-dependent diabetic woman developed phosphate depletion, nephrolithiasis and bilateral ureteric obstruction due to antacid abuse. Unlike previous descriptions of chronic phosphate depletion, myalgia, weakness and bone pain were absent. Biochemical features included hypophosphataemia, hypercalciuria, hypophosphaturia, elevated plasma, 1,25-dihydroxyvitamin D and low plasma intact parathyroid hormone. These abnormalities were corrected when antacid ingestion was reduced and phosphate intake supplemented. We propose that phosphate depletion secondary to antacid abuse caused 1 alpha-hydroxylase activation and elevation of the plasma 1,25-dihydroxyvitamin D level, leading to marked hypercalciuria. Once diagnosed, antacid abuse is a readily reversible cause of hypercalciuria and renal stones. Moreover, antacid-induced phosphate depletion may present with nephrolithiasis in the absence of musculoskeletal symptoms. This report is intended to draw attention to this important cause of renal stone disease.

Adult↗

PubMed2005

Pseudoxanthoma elasticum and nephrolithiasis.

We report the case of a 42-year-old man with pseudoxanthoma elasticum (PXE) and recurrent bilateral nephrolithiasis. Diagnosis of PXE was made by yellow papules on the neck and ophthalmologic angioid streaks. This diagnosis was confirmed by a skin biopsy (Von Kossa stain) and by genotyping analysis of ABCC6 (homozygous mutation R1138Q). Nephrolithiasis was recurrent and biological investigations showed hypophosphoraemia, hyperphosphaturia, hypercalciuria, normocalcaemia, normal serum parathyroid hormone value, high 1,25-dihydroxy vitamin D value and a renal calcium oxalate stone. ABCC6 encodes for MRP6, a multidrug resistant protein strongly expressed in the liver and kidney. The substrates of the MRP6 remain unknown. As PXE is characterized by calcification of elastic fibres and this patient presents important phosphocalcic anomalies, we discuss the possible implications of MRP6 in the phosphocalcic metabolism.

Adult↗