Conclusion. The equations developed in this study provide a more accurate estimate of GFR, ranging from normal to renal impairment, in both Chinese diabetic and non-diabetic patients, compared to currently available GFR formulae. / Hypothesis/objectives. Type 2 diabetes mellitus is a major health burden associated with increased morbidity and mortality as well as socio-economic impact. A rapid increase in disease prevalence has been reported and predicted in China and other Asian countries. Patients with low and declining GFR and microalbuminuria are at high CVD risk. A simple and precise predictive equation of GFR for Chinese diabetic patients is essential in the light of the growing epidemic of diabetes and CKD in Chinese population both for monitoring and treatment purposes. In this pilot study, a set of accurate, simple and clinically practical equations to predict GFR in Chinese type 2 diabetic patients was established. Their performance was validated using separate samples of diabetic and non-diabetic subjects and compared with other widely used GFR formulae. / Methods. 202 type 2 diabetic patient and 46 non-diabetic patients were enrolled in the study. Of these 135 were randomly selected as the training sample; the remaining 67 diabetic patients and 46 non-diabetic patients constituted 2 validation groups. The prediction equation was developed by stepwise regression applied to the training sample. The equation was then tested and compared with other prediction equation including MDRD and CG equations in the validation samples. / Results. Independent factors associated with GFR included age, serum creatinine concentration, serum urea nitrogen level and serum albumin levels (P < 0.005 for all factors). Two predictive formulae, sRFCD and RFCD, were established. Simplified Renal formula in Chinese Diabetes (sRFCD) Study (ml/min/1.73 m2) is: GFR (for men) = 90400 x (Age)-0.495 (yr) x [ SCr]-1.097 (mumol/l) GFR (for women) = 58983 x (Age)-0.542 (yr) x [SCr]-1.012 (mumol/l) and Renal formula in Chinese Diabetes (RFCD) Study (ml/min/1.73 m2) is: GFR (for men) = 11825 x (Age)-0.494 x [SCr]-1.059 (mumol/l) x [Alb]+0.485 (g/l) GFR (for women) = 34166 x ( Age)-0.489 x [SCr] -0.877 (mumol/l) x [SUN] -0.150 (mmol/l) The multiple regression model explained 89.9% and 89.4% respectively of the variance in the logarithm of GFR. Compared to other GFR formulae, the sRFCD and RFCD formulae showed less bias and were more precise and accurate in estimating GFR in diabetic patients whereas the sRFCD and MDRD formulae showed better performance in non-diabetic patients. / Leung Tak Kei. / "July 2006." / Adviser: Juliana C. N. Chan. / Source: Dissertation Abstracts International, Volume: 68-08, Section: B, page: 5117. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (p. 161-180). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Complicações renais e urológicas incluindo nefrolitíase, cristalúria, cólica renal e lombalgia, são eventos adversos bem conhecidos do indinavir (IDV), um inibidor de protease (IP) largamente utilizado no tratamento de pacientes infectados com o vírus da imunodeficiência humana (HIV). Prévios estudos em ratos demonstraram que o IDV, um potente IP capaz de provocar uma sustentada supressão da carga viral do HIV, induz vasoconstricção renal, diminui a filtração glomerular (RFG) e reduz a excreção urinária de nitrito (NO2-), sugerindo que a vasoconstricção causada pelo IDV deve ser mediada pelo óxido nítrico (NO). Os objetivos deste estudo foram investigar a ocorrência de insuficiência renal (clearance de creatinina < 80ml/min) em pacientes com infecção pelo HIV tratados com terapia anti-retroviral altamente potente incluindo o inibidor de protease IDV, e mensurar a excreção urinária de nitrato (NO3-) nestes pacientes, comparando-os com outro grupo de pacientes tratados com efavirenz (EFV), um inibidor de transcriptase reversa não-análogo de nucleosídeo (NNRTI). No período compreendido entre março de 2000 e outubro de 2003, estudamos 36 pacientes infectados pelo HIV que estavam em terapia com IDV na dose de 800 mg de 8/8 horas por pelo menos 12 meses. Os pacientes foram avaliados para uma variedade de parâmetros clínicos e laboratoriais: idade, peso, tempo de infecção, tempo de uso de IDV, uso de sulfametoxazol-trimetoprim (SMX-TMP) ou sulfadiazina, exames bioquímicos (colesterol total, triglicérides, magnésio, sódio, potássio e creatinina), exame do sedimento urinário, clearance de creatinina, osmolaridade urinária, volume urinário de 24 h, fração de excreção de sódio (FENa), fração de excreção de potássio (FEK) e fração de excreção de água (FEH2O). NO3 urinário foi mensurado em 18 pacientes recebendo terapia anti-retroviral com IDV e 8 pacientes recebendo terapia com EFV. Leucocitúria ocorreu em 78.8% dos pacientes tratados com IDV. Clearance de creatinina diminuído foi observado em 21 pacientes e foi associado com menor peso e uso de derivados de sulfa. Nestes pacientes com diminuição da função renal, também detectamos menor osmolaridade urinária e uma FEH2O mais alta. A excreção urinária de NO3- foi significativamente menor nos pacientes tratados com IDV (908 ± 181) quando comparados aos pacientes do grupo EFV (2247 ± 648, p<0.01). Nossos resultados mostram que insuficiência renal ocorreu em 58% dos pacientes tratados com IDV e foi associada com menor peso corpóreo e uso de derivados de sulfa. A menor excreção urinária de NO3- e as alterações na osmolaridade e FEH2O sugerem que o IDV diminui a produção de óxido nítrico e causa dano tubular, respectivamente. Sugerimos então que os pacientes em uso de IDV sejam monitorados routineiramente para função renal através do clearance de creatinina. / Renal and urological complications including nephrolithiasis, crystalluria, renal colic and flank pain are significant side effects of the HIV protease inhibitor indinavir (IDV), and IDV has been widely used in the treatment of human immunodeficiency virus (HIV) infection. Previous studies in rats demonstrated that IDV, a potent protease inhibitor that causes profound and sustained supression of HIV replication, also induces renal vasoconstriction, decreases glomerular filtration rate (GFR) and reduces urinary excretion of nitrite (NO2-), suggesting that IDV-vasoconstriction may be mediated by nitric oxide (NO). The objectives of this study were to investigate the occurrence of renal failure (creatinine clearance <80ml/min) in human HIV patients treated with highy active antiretroviral therapy (HAART), including IDV, and to measure urinary excretion of nitrate (NO3-) in those patients, comparing it with that of another group of patients treated with the non-nucleoside reverse-transcriptase inhibitor efavirenz (EFV). From March 2000 through October 2003, we evaluated 36 patients infected with HIV who was receiving IDV 800 mg q8h for at least 12 months. The patients were assessed for a variety of clinical and laboratory parameters including age, body weight, duration of infection, time of IDV treatment, trimethoprim/sulfamethoxazole (TMP/SMX) or sulfadiazine use, biochemistry (total cholesterol, triglycerides, magnesium, sodium, potassium and creatinine), urinalysis, creatinine clearance, urine osmolality, 24-hour urine volume, fractional excretion of sodium (FENa), potassium (FEK) and water (FEH2O). Urinary NO3 was measured in 18 IDV-treated patients and compared with that of 8 EFV-treated patients. Leukocyturia occurred in 78.8% of the IDV-treated patients. Reduced creatinine clearance was observed in 21 patients and was associated with lower body weight and sulfa-derivated use. In these renal failure patients, we also detected a lower osmolality and a higher FEH2O. Excretion of NO3- was significantly lower in IDV-treated patients (908 ± 181) than in EFV-treated patients (2247 ± 648, p<0.01). Our data show that renal failure occurred in 58% of IDV-treated patients and was associated with lower body weight and sulfa administration. The lower NO3- excretion suggests that this drug decreases nitric oxide production, and the alterations in osmolality and FEH2O indicate that it also causes tubular damage. Based on our findings, we suggest that the renal function of patients under IDV treatment should be closely monitored with creatinine clearance.

Complicações renais e urológicas incluindo nefrolitíase, cristalúria, cólica renal e lombalgia, são eventos adversos bem conhecidos do indinavir (IDV), um inibidor de protease (IP) largamente utilizado no tratamento de pacientes infectados com o vírus da imunodeficiência humana (HIV). Prévios estudos em ratos demonstraram que o IDV, um potente IP capaz de provocar uma sustentada supressão da carga viral do HIV, induz vasoconstricção renal, diminui a filtração glomerular (RFG) e reduz a excreção urinária de nitrito (NO2-), sugerindo que a vasoconstricção causada pelo IDV deve ser mediada pelo óxido nítrico (NO). Os objetivos deste estudo foram investigar a ocorrência de insuficiência renal (clearance de creatinina < 80ml/min) em pacientes com infecção pelo HIV tratados com terapia anti-retroviral altamente potente incluindo o inibidor de protease IDV, e mensurar a excreção urinária de nitrato (NO3-) nestes pacientes, comparando-os com outro grupo de pacientes tratados com efavirenz (EFV), um inibidor de transcriptase reversa não-análogo de nucleosídeo (NNRTI). No período compreendido entre março de 2000 e outubro de 2003, estudamos 36 pacientes infectados pelo HIV que estavam em terapia com IDV na dose de 800 mg de 8/8 horas por pelo menos 12 meses. Os pacientes foram avaliados para uma variedade de parâmetros clínicos e laboratoriais: idade, peso, tempo de infecção, tempo de uso de IDV, uso de sulfametoxazol-trimetoprim (SMX-TMP) ou sulfadiazina, exames bioquímicos (colesterol total, triglicérides, magnésio, sódio, potássio e creatinina), exame do sedimento urinário, clearance de creatinina, osmolaridade urinária, volume urinário de 24 h, fração de excreção de sódio (FENa), fração de excreção de potássio (FEK) e fração de excreção de água (FEH2O). NO3 urinário foi mensurado em 18 pacientes recebendo terapia anti-retroviral com IDV e 8 pacientes recebendo terapia com EFV. Leucocitúria ocorreu em 78.8% dos pacientes tratados com IDV. Clearance de creatinina diminuído foi observado em 21 pacientes e foi associado com menor peso e uso de derivados de sulfa. Nestes pacientes com diminuição da função renal, também detectamos menor osmolaridade urinária e uma FEH2O mais alta. A excreção urinária de NO3- foi significativamente menor nos pacientes tratados com IDV (908 ± 181) quando comparados aos pacientes do grupo EFV (2247 ± 648, p<0.01). Nossos resultados mostram que insuficiência renal ocorreu em 58% dos pacientes tratados com IDV e foi associada com menor peso corpóreo e uso de derivados de sulfa. A menor excreção urinária de NO3- e as alterações na osmolaridade e FEH2O sugerem que o IDV diminui a produção de óxido nítrico e causa dano tubular, respectivamente. Sugerimos então que os pacientes em uso de IDV sejam monitorados routineiramente para função renal através do clearance de creatinina. / Renal and urological complications including nephrolithiasis, crystalluria, renal colic and flank pain are significant side effects of the HIV protease inhibitor indinavir (IDV), and IDV has been widely used in the treatment of human immunodeficiency virus (HIV) infection. Previous studies in rats demonstrated that IDV, a potent protease inhibitor that causes profound and sustained supression of HIV replication, also induces renal vasoconstriction, decreases glomerular filtration rate (GFR) and reduces urinary excretion of nitrite (NO2-), suggesting that IDV-vasoconstriction may be mediated by nitric oxide (NO). The objectives of this study were to investigate the occurrence of renal failure (creatinine clearance <80ml/min) in human HIV patients treated with highy active antiretroviral therapy (HAART), including IDV, and to measure urinary excretion of nitrate (NO3-) in those patients, comparing it with that of another group of patients treated with the non-nucleoside reverse-transcriptase inhibitor efavirenz (EFV). From March 2000 through October 2003, we evaluated 36 patients infected with HIV who was receiving IDV 800 mg q8h for at least 12 months. The patients were assessed for a variety of clinical and laboratory parameters including age, body weight, duration of infection, time of IDV treatment, trimethoprim/sulfamethoxazole (TMP/SMX) or sulfadiazine use, biochemistry (total cholesterol, triglycerides, magnesium, sodium, potassium and creatinine), urinalysis, creatinine clearance, urine osmolality, 24-hour urine volume, fractional excretion of sodium (FENa), potassium (FEK) and water (FEH2O). Urinary NO3 was measured in 18 IDV-treated patients and compared with that of 8 EFV-treated patients. Leukocyturia occurred in 78.8% of the IDV-treated patients. Reduced creatinine clearance was observed in 21 patients and was associated with lower body weight and sulfa-derivated use. In these renal failure patients, we also detected a lower osmolality and a higher FEH2O. Excretion of NO3- was significantly lower in IDV-treated patients (908 ± 181) than in EFV-treated patients (2247 ± 648, p<0.01). Our data show that renal failure occurred in 58% of IDV-treated patients and was associated with lower body weight and sulfa administration. The lower NO3- excretion suggests that this drug decreases nitric oxide production, and the alterations in osmolality and FEH2O indicate that it also causes tubular damage. Based on our findings, we suggest that the renal function of patients under IDV treatment should be closely monitored with creatinine clearance.