Adenine phosphoribosyl transferase deficiency leads to renal allograft dysfunction in kidney transplant recipients: a systematic review / A deficiência de adenina fosforibosiltransferase leva à disfunção do aloenxerto renal em receptores de transplante renal: uma revisão sistemática

Abstract Background: Adenine phosphoribosyl transferase (APRT) deficiency has great implications on graft survival in kidney transplant patients. This systematic review investigated the diagnostic pattern, treatment approach, and kidney transplant outcomes among kidney transplant patients with adenine phosphoribosyl transferase deficiency. Material and methods: Articles reporting the APRT enzyme deficiency and kidney allograft dysfunction were retrieved from PubMed/Medline, ScienceDirect, Cochrane library and Google scholar databases. Descriptive analysis was used to draw inferences. Results: The results from 20 selected studies covering 30 patients receiving 39 grafts had an average age of 46.37 years are presented. Graft survival time of more than 6 months was reported in 23 (76.7%) patients, while other 7 (23.3%) patients had graft survival time of less than 6 months. Only 4 (13.3%) patients had APRT deficiency before transplantation. After follow-up, one-third of the patients 10 (33.3%) had stable graft function, 1 patient had allograft loss, 8 (26.6%) patients had delayed graft function while the remaining 11 (36.6%) patients had chronic kidney graft dysfunction. Conclusions: APRT deficiency is an under-recognized, treatable condition that causes reversible crystalline nephropathy, leading to loss of allograft or allograft dysfunction. The study results showed that inclusion of genetic determination of APRT deficiency in the differential diagnosis of crystalline nephropathy, even in the absence of a history of nephrolithiasis, can improve renal outcomes and may improve allograft survival.

Resumo Antecedentes: A deficiência de adenina fosforibosiltransferase (APRT) tem grandes implicações na sobrevida do enxerto em pacientes transplantados renais. Esta revisão sistemática investigou o padrão diagnóstico, a abordagem de tratamento e os desfechos do transplante renal entre pacientes transplantados renais com deficiência de adenina fosforibosiltransferase. Material e métodos: Os artigos que relatam sobre a enzima APRT e a disfunção do aloenxerto renal foram recuperados do PubMed/Medline, ScienceDirect, Biblioteca Cochrane e bancos de dados do Google Acadêmico. Utilizou-se a análise descritiva para extrair inferências. Resultados: Foram incluídos participantes que receberam 39 enxertos, a maioria dos quais provenientes de doadores vivos seguidos por doadores falecidos e doadores cadáveres. Foi relatado tempo de sobrevida do enxerto superior a 6 meses em 23 (76,7%) pacientes, enquanto outros 7 (23,3%) pacientes tiveram tempo de sobrevida do enxerto inferior a 6 meses. Apenas 4 (13,3%) pacientes apresentaram deficiência de APRT antes do transplante. Após acompanhamento, um terço dos pacientes, 10 (33,3%) apresentaram função do enxerto estável, 1 paciente teve perda do aloenxerto, 8 (26,6%) pacientes apresentaram função retardada do enxerto, enquanto os 11 (36,6%) pacientes restantes tiveram disfunção crônica do enxerto renal. Conclusões: A deficiência de APRT é uma causa subestimada e reversível de nefropatia cristalina que leva à disfunção do aloenxerto renal ou à perda total do aloenxerto. Os resultados deste estudo pedem a inclusão desta condição no diagnóstico diferencial de nefropatia cristalina, mesmo na ausência de um histórico de nefrolitíase.

Adverse drug reactions & their risk factors among Indian ambulatory elderly patients.

Background & objectives: Several studies have reported adverse drug events ranging from 5 to 35 per cent in all age group from outpatient setting. However, adverse drug reactions (ADRs) particularly among a large sample of ambulatory elderly patients in India has not been reported. This study has attempted to identify ADRs and assessed their causality, preventability and severity, and also their risk factors in Indian ambulatory elderly patients. Methods: A 2 year long term prospective study included 4005 ambulatory elderly patients (60 yr or above; either sex) at a public teaching hospital. Suspected ADRs were assessed for causality, preventability and severity using Naranjo's probability scale, modified Schumock and Thornton's criteria, and modified Hartwig's criteria, respectively. Results: Of the total 4005 prescriptions, 406 were identified with ADRs, giving the occurrence of 10 per cent ADRs in elderly. The total number of ADRs was 422 in 406 prescriptions. Type A ADRs accounted for 46 per cent of the total ADRs. Majority of the ADRs (88.6%) were classified as ‘probable’. The definitely preventable reactions were 22 per cent. The percentage of moderate reaction was 16 per cent. Only 1.6 per cent ADRs was severe in nature. The most common type of ADR was peripheral oedema. The most commonly offending class of drug was cardiovascular drugs (57.6%). Using logistic regression analysis, the risk factors which contributed to ADRs were age above 80 yr (OR=1.7), prescription of multiple drugs (OR=1.8), longer duration of treatment (OR=2.28) and multiple diagnoses (OR=1.8). Interpretation & conclusions: In this study, 10 per cent ambulatory elderly patients were found to have ADRs. This indicates that the elderly patients should be closely monitored for ADRs, to avoid clinically significant harmful consequences. The awareness of risk factors of ADRs would help physicians to identify elderly patients with greater risk of ADRs and, therefore, might benefit from ADRs monitoring and reporting programme.

Supported and unsupported claims in medicinal drug advertisements in Indian medical journals.

The study assessed 292 supported and unsupported claims in 102 medicinal drug advertisements across 15 Indian medical journals published in 2009. WHO ethical criteria for medicinal drug promotion were applied. None of the advertisements satisfied all the WHO criteria. Safe prescribing information on major adverse drug reactions, contraindications and warnings was provided in only 19 advertisements.

Prevalence & determinants of depression in type 2 diabetes patients in a tertiary care centre.

Background & objectives: Depression is common among people with diabetes and it is associated with poor outcomes. This study was carried out to investigate the prevalence and determinants of depression in patients with established type 2 diabetes (T2DM) attending a tertiary care hospital in north India. Methods: Patients with established T2DM were evaluated for depression by administering the nine-item PHQ-9 (Hindi version). Binary logistic regression model was used to examine association between predictor variables and risk of depression. Results were expressed as odds ratio and 95 per cent confidence interval. Cronbach alpha was calculated to assess internal consistency of PHQ-9. Results: Patients with T2DM (n=300) were evaluated [147(49%) male and 153(51%) female]. The median duration of diabetes (IQ) was 8(4-13) yrs. Of the study patients, 68 (23%) met the criteria for major depression, 54 (18%) for moderate depression and the remaining 178 (59%) had no clinically significant depression. Depression was strongly associated with age >54 yr (OR 1.26, 95% CI 1.02-1.67; P<0.05), central obesity (OR 1.34, 95% CI 1.04-1.64; P<0.001), neuropathy (OR 1.94, 95% CI 1.03-3.66; P=0.002), nephropathy (OR 1.81, 95% CI 1.02-3.21; P=0.041), peripheral vascular disease (OR 6.08, 95% CI 1.07-34.6; P=0.042), diabetic foot disease (OR 2.32, 95% CI 1.06-5.86; P<0.001) and pill burden (>4) (OR 1.27, 95%CI 1.01-1.44; P=0.035 ). However, the likelihood of depression was not significant with duration of diabetes and insulin use. Interpretation & conclusion: This study showed high prevalence of depression in patients with T2DM. The risk factors for depression were age, central obesity, diabetic complications particularly neuropathy and diabetic foot disease and increased pill burden.

Predictors of metabolic syndrome in Asian north Indians with newly detected type 2 diabetes.

Background & objectives: The identifi cation of metabolic syndrome (MS) among patients with type 2 diabetes (T2DM) is of great importance, since those with MS carry a cluster of cardiovascular risk factors. This study evaluates suitable criteria with high effi ciency in diagnosing MS and to identify the strongest predictors of MS in newly detected type 2 diabetes individuals. Methods: Newly detected type 2 diabetes (<6 months) patients were assessed. The MS was assessed by WHO, National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III), modifi ed NCEP-ATP-III and International Diabetes Federation (IDF) criteria. Receiver operating characteristics (ROC) curves of serum triglycerides, HDL, and waist circumference were created for the prediction of MS and the area under the corresponding curves (AUC) were used to evaluate the predictive effi ciency of each MS parameter. Different cut points in the selected variables and the corresponding sensitivity, specifi city, positive predictive value (PPV) and negative predictive value (NPV) were estimated. Results: Among the 563 newly detected T2DM individuals, the presence of MS ranged from 57 to 68 per cent according to the different criteria. The higher percentage of MS was observed in modifi ed NCEPATP III criteria. In comparison to men, presence of MS was higher in women in all the four criteria [198 (67%) vs. 165 (62%); 209 (70%) vs. 111 (42%); 231 (78%) vs. 151 (57%); 222 (75%) vs. 129 (49%)] by modifi ed WHO, NCEP-ATP III, modifi ed NCEP-ATP III, and IDF, respectively. The predictive ability to diagnose MS was highest with modifi ed NCEP-ATP III and lowest with IDF criteria. The optimal cut-off of waist circumference in men and women were 90 and 88 cm respectively. Serum triglyceride in men effectively indicated the presence of MS in newly detected T2DM individuals, whereas, in women the HDL-C was the stronger predictor of MS. Interpretation & conclusions: The study results show that modifi ed NCEP-ATP III criteria predict highest occurrence of MS in newly detected T2DM patients. Elevated serum triglyceride for men and decreased serum HDL-C in women were the strongest single predictors, effectively indicating presence of MS in newly detected T2DM.

Prevalence and predictors of metabolic syndrome in non-obese Asian Indians with newly detected type 2 diabetes mellitus.

We measured the prevalence and have evaluated the sensitivity, specificity, positive and negative predictive value of different predictors according to different standard criteria for metabolic syndrome in non-obese newly detected type 2 diabetes. Two hundred and fifteen patients of BMI <25 kg/m2 were studied. Metabolic syndrome prevalence was high in non-obese newly detected type 2 diabetes mellitus individuals. Greater prevalence of metabolic syndrome was observed in modified WHO (50.23%) and lesser in IDF (30.69%) classification. Non-obese metabolic syndrome individuals display significantly higher BMI, per cent body fat, waist circumference, hip circumference, waist hip ratio, blood pressure, triglyceride and a lower high density lipopratein than non-obese individuals without metabolic syndrome. The cut-off point for waist circumference in men was 86 cm and 79.7 cm for women (modified ATP III). Elevated serum triglyceride for men and low serum high density lipoprotein in women were the strongest predictors that effectively indicated the presence of metabolic syndrome in non-obese individuals.