Review of post bariatric surgery effects on common genitourinary physiology

ABSTRACT Background: Obesity is a worldwide challenging health problem. Weight loss through medical management of obesity has not always been successful, thus, giving rise to the need for surgical intervention. Bariatric surgery has been shown to be helpful for morbidly obese patients. However, studies have also shown the effect of surgery on stone formation, fertility and erectile function. This review summarizes the main findings of several studies that analyze stone formation and fertility in men as well as erectile function post bariatric surgery. The underlying pathophysiologic alterations post bariatric surgery include increased absorption of oxalate leading to hyperoxaluria, hypocitraturia and increased urinary calcium oxalate supersaturation. Contradicting data exist on the effect of bariatric surgery on fertility and erectile function. Further studies are needed to analyze the mechanisms.

Valores de referencia de oxalato, calcio, citrato, ácido úrico, fósforo, magnesio, sulfato y sodio urinarios en alumnos de la carrera de bioquímica de la Universidad Nacional del Litoral, Argentina / Reference values for urinary oxalate, calcium, citrate, uric acid, phosphate, magnesium, sulphate and sodium in biochemistry students at Universidad Nacional del Litoral, Argentina

INTRODUCCIÓN: La urolitiasis (UL) es una alteración frecuente, cuya incidencia ha aumentado en el último cuarto del siglo XX. Para su diagnóstico se realizan estudios metabólicos para lo cual es necesario contar con valores de referencia (VR) establecidos para la población en cuestión. OBJETIVO: El objetivo del trabajo fue determinar VR de calcio, oxalato, citrato, úrico, fósforo, magnesio, sulfato y sodio en orina de 24 horas de alumnos de la Facultad de Bioquímica y Ciencias Biológicas de la Universidad Nacional del Litoral, Santa Fe, Argentina. Con los VR hallados se determinó la frecuencia de alteraciones y se la comparó con datos bibliográficos. MATERIAL Y MÉTODOS: Se utilizó la guía NCCLSC28-A3, 2008. La muestra de referencia fue de 69 alumnos. Se utilizaron métodos enzimáticos-colorimétricos, espectrofotómetro Metrolab 1600 plus, electrodos ion selectivo DIESTRO. RESULTADOS: Los VR hallados (IC 95%) fueron para el oxalato: 1,96-45,08; calcio: 20,65-250,74; citrato: 112,78-666,01; ácido úrico 58,73-782,17; fósforo 238,37-1051,44; magnesio 28,7-146,67 todos en mg/24h; sulfato 3,15-25,18 mmol/24h y sodio 42,81-285,3 mEq/24h. Se encontró un 3% hiperoxaluria, 12% hipercalciuria, 3% hipocitraturia y 6% hiperuricosuria, 6% hiperfosfaturia, 6% hipomagnesuria, 7% hipernatriuria, 0% hipersulfaturia. Los VR comparados mostraron coincidencias para algunos analitos y para otros amplias diferencias. CONCLUSIONES: El diagnóstico de la alteración metabólica para el estudio de UL varía según el valor de referencia utilizado. Adoptar valores establecidos para otras poblaciones, incluidos los de los fabricantes de los kits comerciales, conducen a un diagnóstico que puede no ser acorde a la situación clínica del paciente

INTRODUCTION: Urolithiasis (UL) is a common disease whose incidence increased in the last quarter of the twentieth century. Metabolic evaluation is necessary for diagnosis, which requires the establishment of reference values (RV) for the population in question. OBJECTIVE: To determine the RV for calcium, oxalate, citrate, uric acid, phosphate, magnesium, sulphate and sodium in 24-hour urine belonging to students from the School of Biochemistry and Biological Sciences at Universidad Nacional del Litoral, province of Santa Fe, Argentina. Once RV were established, a frequency of alterations was determined and then compared with literature data. METHODS: The NCCLSC28-A3 guideline (2008) was used. The study group included 69 students. The enzymatic colorimetric method, a Metrolab 1600 plus spectrophotometer and a DIESTRO ion-selective electrode were also employed. Results: The RV found (95 % CI) were the following: oxalate, 1.96-45.08; calcium, 20.65-250.74; citrate, 112.78-666.01; uric acid, 58.73-782.17; phosphate, 238.37-1051.44; magnesium, 28.7-146.67, all these values expressed as mg/24h; sulphate, 3.15-25.18 mmol/24h, and sodium, 42.81-285.3 mEq/24h. These findings emerged as well: hyperoxaluria, 3%; hypercalciuria 12%; hypocitraturia, 3%; hyperuricosuria, 6%; hyperphosphaturia, 6%; hypomagnesuria, 6%; hypernatriuria, 7%, and hypersulphaturia, 0%. When RV were compared, some analyte levels were similar and others showed a considerable difference. CONCLUSIONS: The diagnosis of UL through the study of metabolic changes is different according to the reference value used. Applying reference values established for other populations, including those of commercial kits manufacturers, may lead to a diagnosis which does not match the clinical condition of the patient

Effect of mitochondrial potassium channel on the renal protection mediated by sodium thiosulfate against ethylene glycol induced nephrolithiasis in rat model

Purpose: Sodium thiosulfate (STS) is clinically reported to be a promising drug in preventing nephrolithiasis. However, its mechanism of action remains unclear. In the present study, we investigated the role of mitochondrial KATP channel in the renal protection mediated by STS. Materials and Methods: Nephrolithiasis was induced in Wistar rats by administrating 0.4% ethylene glycol (EG) along with 1% ammonium chloride for one week in drinking water followed by only 0.75% EG for two weeks. Treatment groups received STS, mitochondrial KATP channel opener and closer exclusively or in combination with STS for two weeks. Results: Animals treated with STS showed normal renal tissue architecture, supported by near normal serum creatinine, urea and ALP activity. Diazoxide (mitochondria KATP channel opening) treatment to the animal also showed normal renal tissue histology and improved serum chemistry. However, an opposite result was shown by glibenclamide (mitochondria KATP channel closer) treated rats. STS administered along with diazoxide negated the renal protection rendered by diazoxide alone, while it imparted protection to the glibenclamide treated rats, formulating a mitochondria modulated STS action. Conclusion: The present study confirmed that STS render renal protection not only through chelation and antioxidant effect but also by modulating the mitochondrial KATP channel for preventing urolithiasis.

Studying inhibition of calcium oxalate stone formation: an in vitro approach for screening hydrogen sulfide and its metabolites

Calcium oxalate urolithiasis is one of the most common urinary tract diseases and is of high prevalence. The present study proposes to evaluate the antilithiatic property of hydrogen sulfide and its metabolites like thiosulfate & sulfate in an in vitro model.

Comparison of quality of life between hemodialysis patients waiting and not waiting for kidney transplant from a poor region of Brazil / Comparação da qualidade de vida entre pacientes em hemodiálise aguardando e não aguardando transplante renal em uma região pobre do Brasil

INTRODUCTION: There are few data about the quality of life (QOL) level among patients undergoing hemodialysis (HD) and not eligible for kidney transplant. OBJECTIVE: The QOL level was compared between HD patients waiting and not waiting for kidney transplant. METHODS: We included 161 end-stage renal disease patients undergoing HD, during April, 2009. All patients were older than 18 years old, had been on HD at least three months, and had no previous transplantation. To measure QOL, the SF-36 was used. We also collected data about death and transplants in the 12 months after April, 2009. QOL scores were compared by analysis of variance with covariates. RESULTS: Patients not awaiting transplantation were older (53.7 versus 36.3 years old; p < 0.001), more often had diabetes (15.8 versus 4.7 percent; p = 0.032) and hypertension (35.5 versus 12.9 percent; p < 0.001), and had no lupus (0 versus 4.7 percent; p = 0.001). They also presented lower creatinine levels (11.5 versus 13.5 mg/dL; p = 0.001) and were submitted to a lower dose of dialysis, estimated by Kt/V (1.6 versus 2.0; p = 0.026). Patients not awaiting transplant died more often in the following 12 months (21.1 versus 5.9 percent; p = 0.005). Adjusted mean scores were lower among patients not awaiting transplant regarding six dimensions of QOL: functional capacity (42.0 versus 53.4; p = 0.022), physical limitation (29.9 versus 49.2; p = 0.030); pain (45.0 versus 64.0; p = 0.003), social aspects (56.3 versus 75.9; p = 0.003), emotional aspects (45.1 versus 79.0; p = 0.001), and mental health (50.1 versus 64.3; p = 0.004). CONCLUSIONS: Patients undergoing HD and not awaiting transplant are at risk of poor QOL level, mainly regarding role-emotional and role-physical aspects. We recommend psychological approaches and physical rehabilitation for this group of patients.

INTRODUÇÃO: Há pouca informação acerca do nível de qualidade de vida (QV) entre pacientes em hemodiálise (HD) não-elegíveis para transplante renal. OBJETIVO: Foi comparado o nível de QV entre pacientes em HD inscritos e não-inscritos na lista de espera para transplante renal. MÉTODOS: Foram incluídos 161 pacientes portadores de doença renal crônica terminal, mantidos em HD durante abril de 2009, com mais de 18 anos, mais de três meses em HD e sem realização de transplante prévio. Para medida de QV, utilizou-se o SF-36. Também foram coletados dados sobre óbito e transplante ocorridos nos 12 meses seguintes a abril de 2009. As pontuações de QV foram comparadas pela análise de variância com covariáveis. RESULTADOS: Pacientes que não aguardavam transplante eram mais velhos (53,7 versus 36,3 anos; p < 0,001), tinham mais diabetes (15,8 versus 4,7 por cento; p = 0,032) e hipertensão (35,5 versus 12,9 por cento; p < 0,001) e não apresentavam lúpus (0 versus 4,7 por cento; p = 0,001). Esses pacientes também apresentavam creatinina mais baixa (11,5 versus 13,5 mg/dL; p = 0,001) e eram submetidos a menor dose de diálise, estimada pelo Kt/V (1,6 versus 2,0; p = 0,026). Pacientes que não aguardavam transplante evoluíram mais frequentemente para óbito no período de 12 meses (21,1 versus 5,9 por cento; p = 0,005). As médias ajustadas das pontuações foram mais baixas entre os pacientes que não aguardavam transplante em seis dimensões da QV: capacidade funcional (42,0 versus 53,4; p = 0,022); limitação por aspectos físicos (29,9 versus 49,2; p = 0,030); dor (45,0 versus 64,0; p = 0,003); aspectos sociais (56,3 versus 75,9; p = 0,003); limitação por aspectos emocionais (45,1 versus 79,0; p = 0,001) e saúde mental (50,1 versus 64,3; p = 0,004). CONCLUSÕES: Pacientes em HD que não aguardam transplante estão em risco de vivenciar baixa QV, principalmente no que se refere à limitação por aspectos emocionais e físicos...

Phyllanthus niruri as a promising alternative treatment for nephrolithiasis

In spite of considerable efforts to identify effective treatments for urolithiasis, this is a goal yet to be achieved. This review summarizes experimental and clinical data evaluating the effect of the plant Phyllanthus niruri, a plant with worldwide distribution, as a potential agent to prevent and/or to treat urolithiasis The review is based on data from the literature and on the results obtained by our group from either in vivo/in vitro experiments or clinical studies. Phyllanthus niruri has been shown to interfere with many stages of stone formation, reducing crystals aggregation, modifying their structure and composition as well as altering the interaction of the crystals with tubular cells leading to reduced subsequent endocytosis. The clinical beneficial effects of Phyllanthus niruri may be related to ureteral relaxation, helping to eliminate calculi or to clear fragments following lithotripsy, or also to a putative reduction of the excretion of urinary crystallization promoters such as calcium. No adverse renal, cardiovascular, neurological or toxic effects have been detected in either of these studies. Altogether, these studies suggest a preventive effect of Phyllanthus niruri in stone formation or elimination, but still longer-term randomized clinical trials are necessary to confirm its therapeutic properties.

Effect of biomolecules from human renal matrix of calcium oxalate monohydrate (CaOx) stones on in vitro calcium phosphate crystallization

PURPOSE: Investigate the activity of high and low molecular weight biomolecules present in the matrix of human calcium oxalate (CaOx) stones not only on the initial mineral phase formation of calcium and phosphate (CaP) but also on its growth and demineralization of the preformed mineral phase. MATERIALS AND METHODS: Surgically removed renal stones were analyzed by Fourier Transform Infra Red (FTIR) spectroscopy and only CaOx stones were extracted with 0.05M EGTA, 1 mM PMSF and 1 percent ß-mercaptoethanol. Renal CaOx stone extract was separated into > 10 kDa and < 10 kDa fractions by dialysis. Activity of both the fractions along with whole extract was studied on the three mineral phases of CaP assay system. RESULTS: It was interesting to observe that both high and low molecular weight biomolecules extracted from human renal matrix of calcium oxalate (CaOx) stones exhibited different roles in the three mineral phases of CaP. Whole extract exhibited inhibitory activity in all the three assay systems; however, mixed (stimulatory and inhibitory) activity was exhibited by the > 10 kDa and < 10 kDa fractions. SDS-PAGE analysis showed bands of 66 kDa, 80 kDa, 42 kDa in whole EGTA extract lane and > 10 kDa fraction lane. CONCLUSION: Both high and low molecular weight biomolecules extracted from human renal matrix of calcium oxalate (CaOx) stones have a significant influence on calcium and phosphate (CaP) crystallization.

Effect of Aerva lanata on calcium oxalate urolithiasis in rats.

Calcium oxalate (CaOx) stone was induced in rats using 0.75% of ethylene glycol in drinking water for 28 days. Ethylene glycol treated rats showed significant increase in the activities of oxalate synthesizing enzymes such as glycolic acid oxidase (GAO) in liver and lactate dehydrogenase (LDH) in liver and kidney. CaOx crystal deposition, as indicated by increased excretion of stone-forming constituents in urine, such as calcium, oxalate, uric acid, phosphorus and protein and decreased concentration of inhibitors, such as citrate and magnesium was observed in ethylene glycol induced urolithic rats. Histopathological studies also confirmed the deposition of CaOx crystals. Administration of Aerva lanata aqueous suspension (2g/kg body wt/dose/day for 28 days) to CaOx urolithic rats had reduced the oxalate synthesizing enzymes, diminished the markers of crystal deposition in the kidney. The results of the present study confirmed that A. lanata can be used as an curative agent for urolithiasis.

Effect of renal ischaemia reperfusion on calcium oxalate retention.

The effect of ischaemia reperfusion induced renal injury for calcium oxalate deposition under normal and simulated conditions was studied. Male Wistar rats of both control (group I) and urolithic (group II) groups underwent (1 h) unilateral renal artery occlusion and were subjected to 1, 3, 6, 12, 24 and 72 h reperfusion. The group I rats subjected to 1 h renal ischaemia followed by 3 and 6 h reperfusion had significant oxalate retention than that of sham operated controls. In group II, under hyperoxaluric condition, in addition to accumulation of oxalate, calcium oxalate deposits were also observed. The increased retention of calcium oxalate was attributed to increased oxalate binding protein activity, oxalate synthesizing enzymes lactate dehydrogenase and xanthine oxidase activities and accumulation of calcium. Our findings suggested that renal cellular injury produced by ischaemia reperfusion could accelerate calcium oxalate precipitation reaction.

Mechanisms involved in calcium oxalate endocytosis by Madin-Darby canine kidney cells

Calcium oxalate (CaOx) crystals adhere to and are internalized by tubular renal cells and it seems that this interaction is related (positively or negatively) to the appearance of urinary calculi. The present study analyzes a series of mechanisms possibly involved in CaOx uptake by Madin-Darby canine kidney (MDCK) cells. CaOx crystals were added to MDCK cell cultures and endocytosis was evaluated by polarized light microscopy. This process was inhibited by an increase in intracellular calcium by means of ionomycin (100 nM; N = 6; 43.9 percent inhibition; P<0.001) or thapsigargin (1 µM; N = 6; 33.3 percent inhibition; P<0.005) administration, and via blockade of cytoskeleton assembly by the addition of colchicine (10 µM; N = 8; 46.1 percent inhibition; P<0.001) or cytochalasin B (10 µM; N = 8; 34.2 percent inhibition; P<0.001). Furthermore, CaOx uptake was reduced when the activity of protein kinase C was inhibited by staurosporine (10 nM; N = 6; 44 percent inhibition; P<0.01), or that of cyclo-oxygenase by indomethacin (3 µM; N = 12; 17.2 percent inhibition; P<0.05); however, the uptake was unaffected by modulation of potassium channel activity with glibenclamide (3 µM; N = 6), tetraethylammonium (1 mM; N = 6) or cromakalim (1 µM; N = 6). Taken together, these data indicate that the process of CaOx internalization by renal tubular cells is similar to the endocytosis reported for other systems. These findings may be relevant to cellular phenomena involved in early stages of the formation of renal stones

Effect of vitamin E and mannitol on renal calcium oxalate retention in experimental nephrolithiasis.

The calcium oxalate stone formation is induced in rats by a single injection of sodium oxalate (i.p., 7 mg/100 g body weight). There was increase in kidney oxalate concentration and kidney mitochondrial oxalate binding activity with increased lipid peroxidation. Histopathological observations showed larger aggregates of calcium oxalate crystals in the renal tubules. At 12 hours after oxalate administration a maximal crystal deposition in the renal tubule with denuded epithelium, lymphocytic infiltration and blood were observed. Increased blood urea and creatinine indicated kidney failure after oxalate administration. Calcium oxalate crystalluria, hematuria, and proteinuria with casts were observed. Renal antioxidants vitamin E, ascorbic acid and glutathione were significantly decreased on oxalate challenge. Pretreatment with vitamin E provided only partial protection from calcium oxalate deposition. Pretreatment with vitamin E and mannitol together protected the renal tubules completely from calcium oxalate deposition by normalizing the tissue oxalate concentration and mitochondrial oxalate binding activity and increasing the concentration of antioxidants on oxalate challenge.

Efectos beneficiosos del glicerofosfato de magnesio como tratamiento de la litiasis oxalocálcica en pacientes hipercalciúricos / Beneficial effect the magnesium salt of phosphoglyceric how treatment the lithiasis calcium oxalate in patients hypercalciuria

Para ensayar una nueva alternativa terapéutica de la hipercalciuria con litiasis oxalocálcica recidivante, se utilizó la sal magnésica del ácido glicerofosfórico (GPMg) en 24 pacientes (12 varones y 12 mujeres) con 36 años de edad promedio (rango: 20-63). El tipo de la hipercalciuria fue absortiva (A) o tabular (T) (n= 14 y 10 respectivamente). La dosis de PGMg fue de 3g diarios divididos en dos tomas. Se efectuaron controles clínicos a los 1-3 meses (período I), a los 4-6 meses (período II), a los 7-12 meses (período III). a los 12-18 meses (período IV) con determinaciones de Ca, P, Mg, Na, K, NH4, sulfato creatinina, ácidos úricos, cítrico y oxálico, pH y volumen urinario. Se calculó la saturación urinaria en términos de energía libre para la cristalización (DG) de oxalato de calcio, brushita, estruvita, ácido úrico y urato de sodio por medio del programa de computación EQUIL-AT. En un subgrupo de 7 pacientes (5 A y 2 T) se determinaron además la parathormona (PTH) sérica y el AMP cíclico en suero y orina en condiciones basales y al mes de tratamiento con GPMg. La calciuria disminuyo significativamente en todos los períodos considerados de ambos grupos (A y T). La diuresis se incrementó progresivamente. Otros componentes urinarios no presentaron cambios significativos. La DG para el oxalato de calcio y la brushita cayeron significativamente en todos los períodos. No hubo modificación en la saturación urinaria de los restantes compuestos. No hubo evidencias de hiperparatiroidismo secundario en el subgrupo controlado con determinación de PTH sérica y AMPc nefrógeno. En 7 pacientes tratados durante dos años hubo sólo un episodio de recurrencia. La tolerancia del GPMg fue excelente.