Management of osteoporosis in patients with chronic kidney disease.

Patients with CKD have a 4-fivefold higher rate of fractures. The incidence of fractures increases with deterioration of kidney function. The process of skeletal changes in CKD patients is characterized by compromised bone strength because of deterioration of bone quantity and/or quality. The fractures lead to a deleterious effect on the quality of life and higher mortality in patients with CKD. The pathogenesis of bone loss and fracture is complex and multi-factorial. Renal osteodystrophy, uremic milieu, drugs, and systemic diseases that lead to renal failure all contribute to bone damage in CKD patients. There is no consensus on the optimal diagnostic method of compromised bone assessment in patients with CKD. Bone quantity and mass can be assessed by dual-energy x-ray absorptiometry (DXA) or quantitative computed tomography (QCT). Bone quality on the other side can be assessed by non-invasive methods such as trabecular bone score (TBS), high-resolution bone imaging methods, and invasive bone biopsy. Bone turnover markers can reflect bone remodeling, but some of them are retained by kidneys. Understanding the mechanism of bone loss is pivotal in preventing fracture in patients with CKD. Several non-pharmacological and therapeutic interventions have been reported to improve bone health. Controlling laboratory abnormalities of CKD-MBD is crucial. Anti-resorptive therapies are effective in improving BMD and reducing fracture risk, but there are uncertainties about safety and efficacy especially in advanced CKD patients. Accepting the prevalent of low bone turnover in patients with advanced CKD, the osteo-anabolics are possibly promising. Parathyroidectomy should be considered a last resort for intractable cases of renal hyperparathyroidism. There is a wide unacceptable gap in osteoporosis management in patients with CKD. This article is focusing on the updated management of CKD-MBD and osteoporosis in CKD patients. Chronic kidney disease deteriorates bone quality and quantity. The mechanism of bone loss mainly determines pharmacological treatment. DXA and QCT provide information about bone quantity, but assessing bone quality, by TBS, high-resolution bone imaging, invasive bone biopsy, and bone turnover markers, can guide us about the mechanism of bone loss.

Invasive aspergillosis: an important risk factor on the short- and long-term survival of acute myeloid leukemia (AML) patients.

Invasive aspergillosis (IA) during induction chemotherapy of acute myeloid leukemia (AML) could worsen the prognosis. Our objective was to study how the development of IA during AML interferes with the therapeutic strategy and to evaluate its impact on the short- and long-term survival. Newly diagnosed AML patients between the years 2004 and 2007 were retrospectively analyzed. The outcome was death of the patient. A Cox proportional hazards model with the diagnosis of IA and post-induction response evaluation as the main exposure was fitted. Overall, 262 patients were analyzed and 58 IA were observed. The 2-year survival of patients having had remission of AML was 54% and, for patients with failure of chemotherapy, it was 5% (p < 0.001). The 2-year survival of patients having had IA was 14%, and without IA, it was 32% (p = 0.01). Multivariate analysis showed that IA was associated with a higher risk of death in case of remission compared to no IA (hazard ratio [HR] = 1.66 [1.05-2.65], p = 0.031) and also in case of failure (HR = 6.43, p < 0.001). IA was associated with an increased risk of death for patients if they were either in remission or in failure after induction chemotherapy.

Heavy+light chain monitoring correlates with clinical outcome in multiple myeloma patients.

Novel anti-myeloma agents have improved patient response rates, which are historically based on reductions of the M-protein. These methods can be inaccurate for quantifying M-proteins at low concentrations. We compared the consistency and clinical impact of response assignment by electrophoretic and heavy+light chain (HLC) immunoassays post-consolidation in 463 newly diagnosed patients. The two methods gave similar assignments in patients with partial (PR; 79% agreement) or complete response (⩾CR; 92%). However, in patients achieving very good PR (VGPR) there was poor concordance between methods (45%). Median progression-free survival (PFS) for standard VGPR patients was 34.5 months; HLC responses stratified these patients further into PR, VGPR and ⩾CR, with median PFS of 21.3, 28.9 months and not reached, respectively; P<0.001. At this time, abnormal HLC ratios had better concordance with multiparametric flow cytometry (sensitivity 10-4) (37 and 34% positive, respectively), compared to immunofixation (62% positive). In addition, HLC-pair suppression was identified in 38% of patients and associated with shorter PFS (30.6 months vs not reached; P<0.001). We conclude that HLC monitoring could augment electrophoretic assessments in patients achieving VGPR. The prognostic significance of HLC responses might partly depend on the patients' ability to recover their immune system, as determined by normalisation of HLC measurements.

The impact of haemodialysis-associated variables on lipid profile in Egyptian haemodialysis population.

INTRODUCTION: Haemodialysis (HD) patients appear to have particular susceptibility for cardiovascular (CV) diseases with lipid abnormalities among its significant contributors. However, there is controversy concerning the combined effect on lipid constituents during HD of the three commonly used variables; the type of heparin, dialysis membrane and the constituent of dialysate buffer bases. Consequently, this controlled prospective study was thought of. PATIENTS: Randomly 63 patients were assigned from Urology and Nephrology haemodialysis (HD) unit, Mansoura, Egypt for the planned study. Their mean age was 45.79 +/- 13.11 years. Fourteen patients with end-stage renal disease (ESRD) served as control group for the remaining 49 HD patients. They were subdivided according to the HD duration (< and > 1 year), anticoagulant used (unfractionated [UFH] and low-molecular weight heparin [LMWH, Enoxaparin), membrane type (Hemophane [HP] and polysulfone [PS] membrane) and dialysate buffer bases (bicarbonate versus acetate based). METHODS: Determining the fasting lipid value of total cholesterol (TC) and triglycerides (TG) as well as lipoproteins including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and lipoprotein (a) [Lp (a)] was completed. RESULTS: Bicarbonate dialysate was associated with significantly lower TG (134.7 +/- 11 mg/dl vs. 153 +/- 14 mg/dl, p = 0.004), higher HDL-C (33.1 +/- 3 vs. 28.3 +/- 2, p = 0.0002) and subsequently better atherosclerosis risk ratio [TC/HDL-C (ARR)] (6.02 +/- 0.09 vs. 5.3 +/- 0.9, p = 0.001) despite its insignificant effect on TC and LDL-C. However, logarithm (log) Lp (a) level was significantly higher (1.92 +/- 0.05 vs. 1.82 +/- 0.04 p = 0.001) in comparison with acetate dialysate. Membrane type was not influential in those dialyzed for < 1 year before intervention while after a year of HD, PS (n = 11) compared to HP filters (n = 11) significantly lowered TC (151.7 +/- 16 vs. 172.6 +/- 12, p = 0.003), TG (127.8 +/- 15 vs. 155.7 +/- 15, p = 0.004), LDL-C (122.1 +/- 5 vs. 130.6 +/- 7, p = 0.006) levels as well as ARR (5.9 +/- 0.5 vs. 5.4 +/- 0.3, p = 0.02). Likewise was the reduction in log Lp (a) (1.9 +/- 0.03 vs. 1.8 +/- 0.04, p = 0.002) with insignificant effect on HDL-C. After 6 months, Enoxaparin caused significant improvement of TC (0.0004), TG (p = 0.018), LDL-C (p = 0.006), HDL-C (0.041) and Lp (a) (0.047) compared to UFH. Patients who continued on Enoxaparin for 3 more months displayed an even better attenuation in most of lipid parameters whilst continuation of UFH was insignificant. Switching few patients (n = 4) from UFH to LMWH for 3 months resulted in significant lowering of TC (153 +/- 7 vs. 177.7 +/- 3, p = 0.01), TG (127.5 +/- 5 vs. 137.3 +/- 4, p = 0.03) and LDL-C (124.7 +/- 5 vs. 127.5 +/- 5, p = 0.005). However, switching equal number of patients from LMWH to UFH caused no significant change. CONCLUSION: Dyslipidaemia in Egyptian haemodialysis patients was improved when bicarbonate-based haemodialysis, the use of polysulfone membrane, and more so when the low-molecular weight heparin Enoxaparin were used.

Cardiovascular drug trials: how to examine interaction, and why so.

BACKGROUND: In practice the benefit of cardiovascular medicines is less consistent than it is in clinical trials. This is due to multiple uncontrolled factors that co-determine the efficacy of the new treatment. In statistical terms, they interact with the new treatment. Interaction effects are rarely assessed in cardiovascular trials. OBJECTIVE: To review (1) important factors that may interact with the treatment efficacy, (2) how to examine such factors, and (3) why so. RESULTS: Important factors include (a) possible risk factors such as specific patient characteristics, and concomitant medications, and (b) study-specific aspects such as heterogeneities of investigators, health centres, and individual patients including patient compliance. Such factors can be assessed by comparing subgroups. A common but incorrect approach is the comparison of the significances of difference between treatment modalities in either subgroup. Instead, a direct comparison of effect sizes relative to the standard errors is adequate. As an alternative, regression modelling is adequate and convenient. Results of interaction assessments are post-hoc and, therefore, of an exploratory and unconfirmed nature. So, why should they be performed? In cardiovascular research the effects of patient characteristics and drug-drug interactions on drug efficacies are numerous. It is valuable to account at least post-hoc for such mechanisms. Second, current cardiovascular trials involve heterogeneous health centres, investigators, and patient groups. Accounting for these heterogeneities can be helpful to better predict individual responses in future patients. CONCLUSION: Cardiovascular trials enrolling patient groups at risk for heterogeneity should include at least a post-hoc assessment for interaction. Correct and incorrect methods for that purpose are described. Interaction assessments are helpful to better predict the efficacy/safety of new cardiovascular medicines in the future treatment of subgroups of patients. (Neth Heart J 2007;15:61-6.).

Allogeneic hematopoietic cell transplantation for multiple myeloma in Europe: trends and outcomes over 25 years. A study by the EBMT Chronic Malignancies Working Party.

We describe the use and outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for multiple myeloma (MM) in Europe between January 1990 and December 2012. We identified 7333 patients, median age at allo-HSCT was 51 years (range: 18-78), of whom 4539 (62%) were males. We distinguished three groups: (1) allo-HSCT upfront (n=1924), (2) tandem auto-allo-HSCT (n=2004) and (3) allo-HSCT as a second line treatment and beyond (n=3405). Overall, there is a steady increase in numbers of allo-HSCT over the years. Upfront allo-HSCT use increased up to year 2000, followed by a decrease thereafter and represented 12% of allo-HSCTs performed in 2012. Tandem auto-allo-HSCT peaked around year 2004 and contributed to 19% of allo-HSCTs in 2012. Allo-HSCT as salvage after one or two or three autografts was steadily increasing over the last years and represented 69% of allo-HSCTs in 2012. Remarkable heterogeneity in using allo-HSCT was observed among the different European countries. The 5-year survival probabilities from time of allo-HSCT for the three groups after year 2004 were 42%, 54% and 32%, respectively. These results show that the use of allo-HSCT is increasing in Europe, especially as second line treatment and beyond. There is an unmet need for well-designed prospective studies investigating allo-HSCT as salvage therapy for MM.

Radioisotopic evaluation of renal function in cyclosporine-treated pediatric and adult renal transplant recipients and their living donors. A study of 152 donor-recipient pairs.

Renal function was studied in 2 groups of renal transplant recipients and their donors by technetium-99m diethylenetriamine pentaacetic acid and a gamma camera. The pediatric group (group A) comprised 40 children and their adult kidney donors. The adult group (group B) consisted of 112 consecutive adult renal transplant recipients and their adult donors. All patients received kidneys from living donors and were given the same immunosuppression protocol (PRED plus CSA). Donor glomerular filtration rate (GFR) was determined before nephrectomy and at a mean period of 30 (range 10-50) months after nephrectomy. The graft GFR was measured at 1, 3, 6, and 12 months and at the most recent follow-up visit. Moreover, the functional reserve of the graft was assessed by infusion of dopamine and an amino acid. The postnephrectomy GFR of donors in groups A and B were 74 +/- 18 and 72 +/- 20 ml/min/1.73 m2, respectively. The GFR of pediatric recipients was significantly lower than that of adult recipients at corresponding time points along the course of follow-up. The mean values of graft GFR were 47.6 +/- 20 and 63.8 +/- 29.6 ml/min/1.73 m2 for pediatric and adult recipients, respectively (P < 0.001). Moreover, the graft functional reserve was significantly lower in pediatric recipients. These data demonstrate that adult kidneys transplanted into pediatric recipients have lower GFR than those transplanted into adults, despite corrections for body surface area. Although the reason for this phenomenon is unknown, the observation may have important implications for management of pediatric recipients.

Artificial intelligence: a new approach for prescription and monitoring of hemodialysis therapy.

The effect of dialysis on patients is conventionally predicted using a formal mathematical model. This approach requires many assumptions of the processes involved, and validation of these may be difficult. The validity of dialysis urea modeling using a formal mathematical model has been challenged. Artificial intelligence using neural networks (NNs) has been used to solve complex problems without needing a mathematical model or an understanding of the mechanisms involved. In this study, we applied an NN model to study and predict concentrations of urea during a hemodialysis session. We measured blood concentrations of urea, patient weight, and total urea removal by direct dialysate quantification (DDQ) at 30-minute intervals during the session (in 15 chronic hemodialysis patients). The NN model was trained to recognize the evolution of measured urea concentrations and was subsequently able to predict hemodialysis session time needed to reach a target solute removal index (SRI) in patients not previously studied by the NN model (in another 15 chronic hemodialysis patients). Comparing results of the NN model with the DDQ model, the prediction error was 10.9%, with a not significant difference between predicted total urea nitrogen (UN) removal and measured UN removal by DDQ. NN model predictions of time showed a not significant difference with actual intervals needed to reach the same SRI level at the same patient conditions, except for the prediction of SRI at the first 30-minute interval, which showed a significant difference (P = 0.001). This indicates the sensitivity of the NN model to what is called patient clearance time; the prediction error was 8.3%. From our results, we conclude that artificial intelligence applications in urea kinetics can give an idea of intradialysis profiling according to individual clinical needs. In theory, this approach can be extended easily to other solutes, making the NN model a step forward to achieving artificial-intelligent dialysis control.

Coadministration of ketoconazole and cyclosporine for kidney transplant recipients: long-term follow-up and study of metabolic consequences.

In a prospective randomized study including 100 kidney transplant recipients, we previously reported on the safety and financial benefits of the coadministration of ketoconazole (keto) to cyclosporine (CsA)-treated kidney transplant recipients. In this study, we report on the long-term follow-up of these patients and their control group, as well as possible metabolic consequences of this drug combination. Evaluation of 51 keto-treated patients and their control group (49 patients) included graft function, lipogram, fasting blood glucose, liver function tests, serum calcium, phosphorus, and radiological and histopathologic assessments. Follow-up of these patients for 54 months showed that the CsA dose reduction was 72.9% at 12 months, decreased to 69.3% at the last follow-up. We also found that the mean keto dose required for CsA dose reduction decreased to 82.8 +/- 24.1 mg/d compared with the starting dose (100 mg/d). Diagnosis of acute rejection episodes was similar in both groups. However, in the control group, rejection episodes were more recurrent, with poorer response to treatment. Acute CsA nephrotoxicity was more common in the keto group, but this was encountered more at keto induction and was rapidly reversed on further reduction of CsA doses. Chronic graft dysfunction was statistically significantly less in the keto group during the first year. However, by the end of the study, the difference was not statistically significant. In this study, hepatotoxicity was similar in the two groups. On studying the metabolic consequences, we found that serum cholesterol, low-density lipoprotein, and triglyceride levels were lower in the keto group. Bone mineral contents in both groups were less than the mean values for age- and sex-matched healthy controls. From this study, we conclude that long-term use of low-dose keto in CsA-treated kidney transplant recipients is safe and cost-saving and may induce better graft function. Bone mineral contents, vitamin D blood levels, and lipid profiles are not affected by long-term keto coadministration in CsA-treated kidney transplant recipients.

Prevalence of hantavirus antibody in patients with chronic renal disease in Egypt.

In Egypt, the etiology of chronic renal failure (CRF) is not well defined. A hospital-based case-control study was initiated in February 1998, to determine whether hantavirus infection is involved in chronic renal disease (CRD) in Egypt. The study enrolled 350 study patients with a history of CRF and 695 matched controls with CRD due to renal calculus or renal cancer, but with normal renal functions. Sera from cases and controls were tested for anti-hantavirus IgG using ELISA with a cell-lysate antigen from Hantaan virus prototype strain 76-118. A demographic questionnaire was completed for each study participant. Five of the 350 cases (1.4%), and seven of the 695 controls (1.0%) were antibody-positive to hantavirus, with a titer > or =1:400. The difference in antibody prevalence between the study cases and the control cases was not statistically significant (P = 0.48). All antibody-positive study cases and controls had been exposed to rodents. Data indicated that in Egypt, hantavirus seroprevalence in CRD patients is low, and hantavirus infections do not appear to be a significant cause of CRF.

Clinical significance and long-term evolution of minimal change histopathologic variants and of IGM nephropathy among Egyptians.

In children, the most frequent idiopathic nephrotic syndrome is minimal change nephrotic syndrome (MCNS). Typically, MCNS shows no abnormalities by light microscopy: "nil disease". Beside this classic picture, there are other minor light microscopic abnormalities which are considered as MCNS variants. Our 172 MCNS patients were divided into a nil disease group, two groups of MCNS variants (mild mesangial hypercellularity and mild mesangial thickening) and a fourth group with normal light microscopy and diffuse IgM deposition (IgM nephropathy group). The relation of this fourth group to MCNS is controversial in the literature. Age and serum creatinine were significantly different in the four histologic groups (P=0.03 for age and 0.047 for serum creatinine). Comparing the groups in pairs, it appeared that these significant differences were due to significantly higher age and serum creatinine in the mild mesangial hypercellularity group than in the IgM nephropathy group (P = 0.02 for age and 0.01 for serum creatinine). The groups were similar as regards follow-up creatinine clearance and early and late steroid response. We concluded that mild mesangial hypercellularity may differ from other MCNS forms as regards age at presentation and renal function. We also suggest that IgM nephropathy with normal light microscopy is similar to MCNS.

The effect of extracorporeal high blood flow rate on left ventricular function during hemodialysis--an echocardiographic study.

The effect of increased extracorporeal blood flow rate on left ventricular (LV) function has been studied during volume-controlled bicarbonate hemodialysis. Ten stable patients on chronic hemodialysis, with a mean age of 28 years (range 19-38) were studied using two-dimensional and Doppler echocardiography. The mean time on hemodialysis was 32 months (range 3-60). All patients were investigated during three dialysis sessions on the first day of the week for 3 consecutive weeks. The blood flow rate was chosen randomly as 250, 350, or 450 cc/min. Apart from the time of hemodialysis and blood flow rate, other parameters of the hemodialysis were kept stable during all three sessions. Echocardiographic studies were done before, at mid dialysis, and during the last 15 min of each dialysis session. The following parameters were evaluated: heart rate, mean blood pressure, shortening fraction, ejection fraction, cardiac output, and pre-ejection period/LV ejection time ratio. The changes of the measured cardiac parameters at the beginning, middle and end of each session were not significantly different. Furthermore, the differences in changes between the three different sessions were comparable. Our results indicate that an increase in dialysis blood flow rate up to 450 cc/min does not have an adverse effect on the left ventricle in patients on maintenance hemodialysis and with stable cardiovascular function.

Effect of high-dose intravenous immunoglobulin on suppression of alloantibodies against hla in highly sensitized transplant candidates.

Sensitization can present a virtually insurmountable barrier to kidney transplantation. Ten to twenty percent of patients on waiting lists for renal transplantation have developed broadly reactive cytotoxic antibodies against HLA antigens caused by pregnancy, blood transfusion, or a prior failed allograft. These sensitized end-stage renal disease patients often wait more than 5 years for a kidney to be offered. Potent immunosuppressives, plasma exchange and/or immunoadsorption have been used but the risk of infection limited their use. Some reports, have demonstrated in small numbers of patients the use of Intravenous Immunoglobulin (IVIG) as potential modality for the treatment of these sensitized patients. The goal of this study was to investigate the extent of the efficacy and to assess the utility of this modality of treatment on a relatively larger number of patients. The study included 11 patients with end stage renal disease who were waiting for living related renal allotransplantation. All patients had persistently positive crossmatches with their living related donors and PRA titer >/=20%. They received IVIG for a period of two weeks and a total of 6 doses. None of these patients, however, attained significant suppression of anti-HLA antibodies titer or a negative crossmatch reaction. We found that IVIG alone couldn't effectively inhibit preformed anti-HLA antibodies to allow successful renal transplantation.

Human ochratoxicosis and nephropathy in Egypt: a preliminary study.

This preliminary study was designed in a trial to delineate the size of the problem of ochratoxicosis and its relation to genesis of lesions mounting to end stage renal disease (ESRD) or urothelial tumors in Egypt. This study comprised five groups of patients having renal diseases of different presentations; they are: patients with (ESRD) under conservative medical treatment (group 1), patients with (ESRD) under treatment with regular hemodialysis (group 2), renal allograft recipients (group 3), patients with nephrotic syndrome (group 4) and patients with urothelial tumors (group 5). In addition, two reference groups: potential related donors for renal transplantation (group 6) and healthy control with negative family history of renal disease (group 7). For all groups, laboratory, radiological and histopathological evaluation of kidney status were carried out coupled with determination of ochratoxin A level in serum, in urine and in biopsy specimens of patients with urothelial tumors. High ochratoxin serum levels were found in patients with ESRD (groups 1 and 2) (P < 0.01), higher serum levels were detected in the group without dialysis (group 1) in comparison with the reference groups possibly due to ochratoxin. A clearance by dialysis. Ochratoxin A was detected in serum and urine of renal transplant recipients (group 3) (P < 0.01) and especially higher levels were found in patients with nephrotic syndrome (group 4) (P < 0.001). For the group with urothelial tumor (group 5), positive serum, urine and tissue biopsy specimens for ochratoxin levels were found (P < 0.01). The results could lead to the conclusion that ochratoxin A could be correlated to the genesis of renal disease leading to (ESRD) or causing urothelial cancer. A thorough and in depth study of the problem of ochratoxicosis and renal disease causation in Egypt is now recommended.

Bone loss in pediatric renal transplant recipients.

The factors that affect bone mineral density (BMD) and the long term progress of BMD after transplantation in children is still unknown. Therefore we performed a cross-sectional study to determine BMD in 83 recipients who received living renal allotransplants in Mansoura Urology & Nephrology Center between 1981 and 2001 (mean age at transplantation 13.2 +/- 3.1 years) by dual energy x-ray absorptiometry at various time intervals up to 16 years after transplantation (mean duration after transplantation was 48 +/- 34 months, range 6-192 months). The Z-score for lumbar spine was -2.28 +/- 2.06 and -1.44 +/- 1.44 for the total body. Osteopenia/osteoporosis were present in about two thirds of our kidney transplant recipients. The significant predictors for osteopenia/osteoporosis by univariate analysis were cyclosporine based immunosuppression, the cumulative steroid dose/m2 surface area, graft dysfunction and the urinary deoxypyridinoline. Using logistic regression analysis the cumulative steroid dose/m2 surface area and the urinary deoxypyridinoline were the major significant predictors for bone loss.

Value of renal biopsy in chronic renal failure.

A total of 120 patients with chronic renal failure secondary to parenchymatous kidney disease were biopsied. Percutaneous approach was tried and open technique was employed when there was contraindication to or failure of the percutaneous technique. In 72 cases the histopathologic lesions were identified, in 30 cases it was not possible to identify them and in 18 cases there was no sufficient kidney tissue. The diagnosis was very critical in at least 10 cases: there were 3 cases of primary oxalosis, one case of haemolytic uraemic syndrome, one case of necrotizing glomerulonephritis, one case of Wagner's granulomatosis, 3 cases of focal segmental glomerulosclerosis and one case of Fabry's disease. All but one of these were not diagnosed clinically. There was no patient mortality, and morbidity was significantly higher after open approach. We concluded that kidney biopsy in patients with chronic renal failure is mandatory especially if they are going to be transplanted and it is relatively safe especially when the percutaneous technique is employed.

Heme biosynthesis and porphyrin studies in chronic renal failure patients following kidney transplantation.

El-Far and Sobh were the first to describe abnormalities in porphyrin metabolism in Egyptian patients with chronic renal failure (CRF). Our results were confirmed by others. The present investigation aims to study and discuss the nature of those abnormalities and changes in porphyrin metabolism in CRF patients following kidney transplantation. Blood samples and urine were collected from patients (with and without polycythaemia) as well as from normal controls. The activity of heme enzymes such as ALA-S, ALA-D, URO-S, PBGase and URO-D were assayed. Total blood porphyrins as well as enzyme activities such as ALA-S and URO-S were found to be highly significantly increased in all patients, while URO-D activity remained within normal range. The observed elevated erythrocyte porphyrins may be mainly due to increased activity of ALA-S, the rate-limiting enzyme in heme synthesis. The present study is the first of its kind which clearly demonstrates that successful kidney transplantation does not correct or rectify the abnormalities in porphyrin metabolism.

Protective effect of verapamil on ischaemic renal injury in dogs.

Three groups of female mongrel dogs were used. In each dog right nephrectomy was performed. In the first group, 60-min complete occlusion of the left renal artery was followed by 50.4% reduction in RBF (P less than 0.05), 53.4% reduction in GFR (P less than 0.01) and 46.7% reduction in urine flow rate (UV) (P less than 0.05). These haemodynamic changes were accompanied by a significant (P less than 0.01) increase in urinary enzyme activity. In the second group, following Verapamil 0.5 mg/kg i.v. bolus, there was diuresis and natriuresis, urine flow rate (UV) increased by 39% and UNaV by 60% (P greater than 0.05); there were no changes in RBF or GFR. In the third group, pretreatment with Verapamil prior to the arterial occlusion modified the deleterious effects of the 60-min renal ischaemia. RBF decreased by 9.4%, GFR by 28.5% and UV by 11.1% (P greater than 0.05); there was no change in the urinary enzyme activity. It is concluded that Verapamil can protect against ischaemic renal damage.

Cyclosporine in the treatment of steroid resistant rejection episodes in living donor kidney transplants.

Cyclosporine had been used to treat steroid resistant rejection episodes in 24 living related donor kidney transplants. The rejection episodes as well as their response to cyclosporine were documented by graft biopsies and/or fine needle aspiration cytology. Ten similar patients suffering from steroid resistant rejection episodes were not given cyclosporine. These cases were evaluated and their outcome was compared to those who received cyclosporine therapy. In the 24 cases who received cyclosporine, there was complete reversal of the rejection episodes in 11, partial reversal in 6, arrest of the rejection crisis in 4 and failure in 3. In all the 10 cases without cyclosporine therapy the grafts were found to be lost. It was concluded that cyclosporine can cure established rejection episodes even when severe and steroid resistant.

Alterations of plasma free amino acids in nephrotic syndrome.

In order to assess the plasma amino acid pattern in nephrotics, we studied 19 nephrotic patients in good general and nutritional conditions. The results were compared with those of 8 healthy controls of matched age and sex. A highly significant rise of plasma glutamic acid and hydroxyproline was detected in nephrotics. When the latter group is divided into 2 subgroups according to the serum creatinine level, the rise in plasma values of both amino acids was detected in both subgroups compared to the controls, while an insignificant rise was detected in cases with elevated serum creatinine compared to those with normal serum level. So we conclude that there is an alteration in the amino acid pattern in nephrotics, and that this alteration occurs early, before the rise in serum creatinine.