Use of non-irradiated blood components in Campath (alemtuzumab)-treated renal transplant patients.

BACKGROUND: The prevention of transfusion-associated graft-versus-host disease (TA-GvHD) through the irradiation of components is key as there is no effective treatment. Universal leucodepletion reduces but may not eliminate TA-GvHD; therefore, irradiation is still recommended. In 2010, Campath (alemtuzumab) was added as an indication for irradiation but was not implemented everywhere. OBJECTIVES: To identify any cases of TA-GvHD in our Campath-conditioned renal transplant patients, who were transfused with non-irradiated components. METHODS: Retrospective study of Campath-conditioned renal transplant patients transfused with non-irradiated components. In those transfused up to 9 months following Campath who survived to 1-year follow-up, TA-GvHD was excluded. For patients not followed-up for a full year, we reviewed medical records for features of TA-GvHD. For patients transfused after 9 months following Campath, survival of at least 3 months following last transfusion excluded TA-GvHD. RESULTS: Six hundred and forty-seven Campath-conditioned renal transplant patients were transfused; 616 were transfused within 9 months following Campath; 601 were alive at 1 year, excluding TA-GvHD. Twelve died and three were not followed-up for a full year, but a review of medical records excluded TA-GvHD. The 31 patients transfused 9 months or longer following Campath were all alive 6 months following the last transfusion, excluding TA-GvHD. CONCLUSIONS: Despite receiving non-irradiated components, none of the 647 Campath-conditioned renal transplant patients developed TA-GvHD. Further reviews to replicate our data could enable change to guidance, at least in UK where components are leucodepleted, as an unnecessary requirement for irradiated components has both clinical delay and cost implications.

A Systematic Review of Outcomes Following Percutaneous Transluminal Angioplasty and Stenting in the Treatment of Transplant Renal Artery Stenosis.

PURPOSE: To evaluate outcomes following treatment of transplant renal artery stenosis by percutaneous transluminal angioplasty and stent insertion. MATERIALS AND METHODS: A literature search was performed using Pubmed, MEDLINE, Embase, Wiley Interscience and the Cochrane Library databases. Outcome measures were glomerular filtration rate, creatinine, blood pressure and number of antihypertensive medications. Technical and clinical success, patency and complication rates were also analysed. RESULTS: Thirty-two studies met the inclusion criteria, involving a total of 884 interventions including PTA, stenting, or combinations of both. Clinical success rates were in the range 65.5-94%. The majority of studies reported technical success rates higher than 90%. Patency rates were in the range of 42-100%. However, the definition and diagnostic criteria for TRAS varied widely between studies. Also, marked heterogeneity was observed in the reporting of outcome measures with no consensus in outcome criteria or follow up schedule. CONCLUSION: Outcomes following PTA and stenting for the treatment of TRAS have been shown to be favourable. However, there is a distinct lack of well designed studies assessing outcomes following intervention. Outcome reporting may be improved by the introduction of standardised outcome measures with reporting of outcomes into a multi-centre registry.

Generic tacrolimus in solid organ transplantation.

The availability of a wide range of immunosuppressive therapies has revolutionized the management of patients who have undergone solid organ transplantation (SOT). However, the cost of immunosuppressive drugs remains high. This situation has led to the development of generic equivalents, which are similar in quality, safety, and efficacy to their approved innovator drugs. There are data available for three generic brands, tacrolimus (Intas), tacrolimus (PharOS), and tacrolimus (Sandoz). Bioequivalence has been demonstrated for generic tacrolimus (Sandoz) within a narrow therapeutic range to its innovator tacrolimus drug (Prograf) in both healthy volunteers and kidney transplant patients. Clinical experience with this generic tacrolimus formulation has also been established in both de novo and conversion patients who have undergone kidney and liver transplantation, as well as in conversion of other SOT patients, including lung and heart recipients.

Postanastomotic transplant renal artery stenosis: association with de novo class II donor-specific antibodies.

In this study, we analyze the outcomes of transplant renal artery stenosis (TRAS), determine the different anatomical positions of TRAS, and establish cardiovascular and immunological risk factors associated with its development. One hundred thirty-seven of 999 (13.7%) patients had TRAS diagnosed by angiography; 119/137 (86.9%) were treated with angioplasty, of which 113/137 (82.5%) were stented. Allograft survival in the TRAS+ intervention, TRAS+ nonintervention and TRAS- groups was 80.4%, 71.3% and 83.1%, respectively. There was no difference in allograft survival between the TRAS+ intervention and TRAS- groups, p = 0.12; there was a difference in allograft survival between the TRAS- and TRAS+ nonintervention groups, p < 0.001, and between the TRAS+ intervention and TRAS+ nonintervention groups, p = 0.037. TRAS developed at the anastomosis, within a bend/kink or distally. Anastomotic TRAS developed in living donor recipients; postanastomotic TRAS (TRAS-P) developed in diabetic and older patients who received grafts from deceased, older donors. Compared with the TRAS- group, patients with TRAS-P were more likely to have had rejection with arteritis, odds ratio (OR): 4.83 (1.47-15.87), p = 0.0095, and capillaritis, OR: 3.03 (1.10-8.36), p = 0.033. Patients with TRAS-P were more likely to have developed de novo class II DSA compared with TRAS- patients hazard ratio: 4.41 (2.0-9.73), p < 0.001. TRAS is a heterogeneous condition with TRAS-P having both alloimmune and traditional cardiovascular risk factors.

Microcirculation inflammation associates with outcome in renal transplant patients with de novo donor-specific antibodies.

In renal transplant patients with de novo donor-specific antibodies (dnDSA) we studied the value of microcirculation inflammation (MI; defined by the addition of glomerulitis (g) and peritubular capillaritis (ptc) scores) to assess long-term graft survival in a retrospective cohort study. Out of all transplant patients with standard immunological risk (n = 638), 79 (12.4%) developed dnDSA and 58/79 (73%) had an indication biopsy at or after dnDSA development. Based on the MI score on that indication biopsy patients were categorized, MI0 (n = 26), MI1 + 2 (n = 21) and MI ≥ 3 (n = 11). The MI groups did not differ significantly pretransplantation, whereas posttransplantation higher MI scores developed more anti-HLA class I + II DSA (p = 0.011), showed more TCMR (p < 0.001) and showed a trend to C4d-positive staining (p = 0.059). Four-year graft survival estimates from time of indication biopsy were MI0 96.1%, MI1 + 2 76.1% and MI ≥ 3 17.1%; resulting in a 24-fold increased risk of graft failure in the MI ≥ 3 compared to the MI0 group (p = 0.003; 95% CI [3.0-196.0]). When adjusted for C4d, MI ≥ 3 still had a 21-fold increased risk of graft failure (p = 0.005; 95% CI [2.5-180.0]), while C4d positivity on indication biopsy lost significance. In renal transplant patients with de novo DSA, microcirculation inflammation, defined by g + ptc, associates with graft survival.

Renal allograft recipients fail to increase interferon-γ during invasive fungal diseases.

Invasive fungal diseases are a major cause of death in renal allograft recipients. We previously reported that adjunctive recombinant human interferon-γ therapy has clinical utility for invasive fungal diseases after renal transplantation. We have now developed a rapid peripheral blood-based quantitative real-time PCR assay that enables accurate profiling of cytokine imbalances. Our preliminary studies in renal transplant patients with invasive fungal diseases suggest that they fail to mount an adequate interferon-γ response to the fungal infection. In addition, they have reduced IL-10 and increased TNF-α when compared to stable renal transplant patients. These preliminary cytokine profiling-based observations provide a possible explanation for the therapeutic benefit of adjunctive human interferon-γ therapy in renal allograft recipients with invasive fungal diseases.

Is there a role for free breathing non-contrast steady-state free precession renal MRA imaging for assessing live donors? A preliminary study.

OBJECTIVE: Accurate pre-operative evaluation of renal vascular anatomy is essential for successful renal harvest in live donor transplantation. Non-contrast renal MR angiographic (MRA) techniques are potentially well suited to the screening of donors; however, their restricted imaging field of view (FOV) has previously been an important limitation. We sought to assess whether the addition of a large FOV balanced fast field echo (BFFE) steady-state free precession (SSFP) sequence to non-contrast SSFP MRA could overcome this problem. Comparison with contrast-enhanced MRA (CE MRA) and findings at surgery were performed. METHODS: 22 potential renal donors each underwent SSFP and CE MRA. 11 out of 22 potential donors subsequently underwent a donor nephrectomy. RESULTS: All images were diagnostic. Both SSFP MRA and CE MRA identified an equal number of arteries. Surgery confirmed two accessory renal arteries, both demonstrated with both imaging techniques. A third accessory vessel was identified with both techniques on a kidney contralateral to the donated organ. 6 out of 11 procured kidneys demonstrated early branch arteries at surgery, 5 out of 6 of which had been depicted on both SSFP and CE MRA. The median grading of image quality for main renal arteries was slightly better for CE MRA (p=0.048), but for accessory vessels it was better for SSFP MRA. CONCLUSION: This pilot study indicates that by combining free-breathing SSFP MRA with large-FOV bFFE images, an accurate depiction of renal vascular anatomy without the need for intravenous contrast administration can be obtained, as compared with surgical findings and CE MRA.

Outcome of patients with preformed donor-specific antibodies following alemtuzumab induction and tacrolimus monotherapy.

It has been shown that low-level preformed donor-specific antibodies (DSAbs) detected by luminex beads in the setting of a negative CDC and flow cytometry crossmatch (CDC/FCXM) are associated with inferior allograft outcomes. The relevance of preformed DSAbs in patients receiving alemtuzumab induction and tacrolimus monotherapy has not been studied. Four hundred and eighty renal transplant recipients with a negative CDC/FCXM had their pretransplant sera retrospectively screened for DSAbs. 45/480 (9.4%) of patients were found to have preformed DSAbs. Females and patients receiving regrafts were more likely to have a DSAb (p = 0.008 and p < 0.0001, respectively). Patients with DSAbs had inferior allograft survival (p = 0.047), increased incidence of antibody-mediated rejection (p < 0.0001) and inferior allograft function at 6 months posttransplant (p = 0.017). Patients with HLA class I DSAb (alone or in combination with a Class II DSAb) with high mean fluorescence intensities (MFIs) were at highest risk. We conclude that patients with preformed DSAb are at high risk of adverse outcomes when receiving a minimal immunosuppressive regime incorporating alemtuzumab induction. Patients found to have a preformed DSAb despite a negative crossmatch might benefit from augmented immunosuppression.

Recurrence of complement factor H-related protein 5 nephropathy in a renal transplant.

Complement factor H-related protein 5 (CFHR5) nephropathy is a familial renal disease endemic in Cyprus. It is characterized by persistent microscopic hematuria, synpharyngitic macroscopic hematuria and progressive renal impairment. Isolated glomerular accumulation of complement component 3 (C3) is typical with variable degrees of glomerular inflammation. Affected individuals have a heterozygous internal duplication in the CFHR5 gene, although the mechanism through which this mutation results in renal disease is not understood. Notably, the risk of progressive renal failure in this condition is higher in males than females. We report the first documented case of recurrence of CFHR5 nephropathy in a renal transplant in a 53-year-old Cypriot male. Strikingly, histological changes of CFHR5 nephropathy were evident in the donor kidney 46 days post-transplantation. This unique case demonstrates that renal-derived CFHR5 protein cannot prevent the development of CFHR5 nephropathy.

Exogenous interferon-gamma immunotherapy for invasive fungal infections in kidney transplant patients.

The incidence of invasive fungal infections (IFIs) in nonneutropenic solid organ transplant patients is increasing. We report our clinical experience with the use of interferon-gamma (IFN-gamma) immunotherapy in seven renal transplant patients who developed life threatening, disseminated IFIs refractory to conventional antifungal drug therapy. The infections were all microbiologically and histologically proven. The rapid cure of these disseminated infections with exogenous IFN-gamma injections was not associated with impaired kidney allograft function despite the use of liposomal amphotericin B in all cases. No clinical toxicity from the IFN-gamma immunotherapy was seen and no IFI relapsed during long-term follow-up. Our experience is both uncontrolled and in patients with unpredictable fungal infection-related outcomes. However, compared to standard approaches, the accelerated cure of life threatening, disseminated IFIs with 6 weeks of combination antifungal drug therapy and IFN-gamma immunotherapy saved lives, retained allograft function and led to substantial cost savings in this small patient group.

Effects of long-term elevated glucose on collagen formation by mesangial cells.

Glomerulosclerosis is one of the complications of diabetes that occurs after many years of uncontrolled hyperglycemia. Mesangial cells (MCs) exposed to high glucose (HG) for short periods have shown that transforming growth factor-beta (TGF-beta) and activated diacylglycerol-dependent protein kinase C (PKC) mediate increased collagen formation. Our study examined collagen formation by MCs exposed to HG for 8 weeks. Exposure to HG in overnight culture resulted in the activation of all PKC isoforms. In contrast, 8-week exposure to HG resulted in the persistent activation of PKC-delta, did not change PKC-alpha or -beta activity, and decreased PKC-epsilon activity while increasing collagen I and IV gene and protein expression. Collagen IV accumulation was reversed by specific PKC-delta inhibition. Collagen IV gene expression was completely normalized by TGF-beta neutralization; however, this was associated with plasminogen activator inhibitor-1 (PAI-1) overexpression and a modest reduction in collagen protein. Our studies suggest that prolonged exposure to HG results in PKC-delta-driven collagen accumulation by MCs mediated by PAI-1 but independent of TGF-beta.

Mycophenolic acid 12-h trough level monitoring in renal transplantation: association with acute rejection and toxicity.

Studies of renal transplantation utilizing trough plasma level monitoring of mycophenolic acid (MPA) have shown inconsistent associations with toxicity and rejection. In this study, 5600 12-h trough MPA samples from 121 renal transplant recipients immunosuppressed with mycophenolate mofetil (MMF) and tacrolimus in a steroid sparing protocol (steroids for 7 days only) were sequentially analyzed. Higher MPA levels were associated with lower hemoglobin concentrations and anemia (hemoglobin <10 g/dL). Similarly, higher MPA levels were associated with lower total white cell counts and an increased incidence of leucopenia (total white cell count <4.0 x 10(9)/L). Hypoalbuminemia and renal impairment were also associated with hemotoxicity. MMF-associated diarrhea and viral infection were associated with higher MPA levels. Conversely, biopsy-proven acute rejection within the first month post-transplantation was associated with lower MPA levels. Anti-CD25 antibody induction was also associated with reduced rejection rates. No association was seen between MPA levels and platelet count, thrombocytopenia or bacterial infection. An MPA level of 1.60 mg/L early post-transplantation best discriminated patients with and without rejection, and an MPA level of 2.75 mg/L best discriminated patients with and without toxicity later post-transplantation.

Tacrolimus monitoring in renal transplantation: a comparison between high-performance liquid chromatography and immunoassay.

It is recommended that specific methods of tacrolimus monitoring rather than immunoassays, which overestimate tacrolimus levels, should be used in transplant recipients. Direct comparison of these techniques, however, has not been conducted in renal transplantation. In this study, 40 renal transplant recipients with tacrolimus monitoring by microparticle enzyme immunoassay (MEIA; target trough level 10 to 15 ng/mL) were compared with 40 patients monitored by high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS; target trough level 8 to 13 ng/mL). All patients received anti CD25 antibody induction and mycophenolate mofetil in a steroid-sparing protocol. No differences were seen between MEIA and HPLC-MS groups in patient demographics. All patients were followed for 6 months. Patient survival was 100% in both groups; graft survival was 100% in the MEIA group and 97.5% in the HPLC-MS group. The groups did not differ in the number of dose changes required in the first 6 months or in the number of patients displaying tacrolimus levels within target range at 3 and 6 months. Delayed graft function occurred in 14 patients in the MEIA group and 12 patients in the HPLC-MS group (P = NS). Biopsy-proven acute rejection occurred in four patients in the MEIA group and one patient in the HPLC-MS group (P < .2). No differences were seen for the following parameters at 3 or 6 months: biopsy-proven tacrolimus nephrotoxicity, serum creatinine or estimated creatinine clearance, systolic or diastolic blood pressure, cholesterol, cytomegalovirus disease, posttransplant diabetes, or tremor. This study suggests that renal transplantation with HPLC-MS monitoring of tacrolimus is safe and effective.

Cytokine polymorphisms do not influence acute rejection in renal transplantation under tacrolimus-based immunosuppression.

INTRODUCTION: Acute rejection remains an important cause of graft loss after renal transplantation. It has been suggested that cytokine genotyping may play a predictive role in identifying individuals who are at higher risk of acute rejection with a view to individualizing their immunosuppression. The aim of this study was to investigate any possible associations between acute rejection and certain cytokine polymorphisms. METHODS: We genotyped 91 cadaveric renal transplant recipients on tacrolimus-based immunosuppression and 84 of their donors. The cytokine polymorphisms studied were the following: tumor necrosis factor (TNF)-alpha-1032 T/C, TNF-alpha-865 C/A, TNF-alpha-859 G/A, interleukin (IL)1-R1-970 C/T, IL-10 haplotype [-1082, -819, -592], and IL-6-174 C/G. RESULTS: We found no association between any polymorphism and the incidence of acute rejection. This was true for both the recipient and donor population. CONCLUSION: Cytokine polymorphisms did not influence acute rejection in our study. We conclude that in the modern era of immunosuppression cytokine genotyping is not a significant predictor of acute rejection in renal transplantation.

Steroid sparing in renal transplantation with tacrolimus and mycophenolate mofetil: three-year results.

Although renal transplantation with a 7-day steroid-sparing regimen, tacrolimus and mycophenolate, is associated with good short-term outcomes, late allograft dysfunction and failure remain concerns. In this study 101 consecutive patients underwent renal transplantation using this immunosuppressive regimen. In addition, anti-CD25 monoclonal antibody was used in 25 high-risk patients (regrafts, two-antigen human leukocyte antigen (HLA)-DR mismatch or sensitized with anti-HLA panel reactivity >30%). After a median follow-up of 39 months (range 29 to 49), overall patient survival is 98%, with two cardiac deaths. Three other graft losses occurred, one each to early venous thrombosis, polyoma viral nephropathy, and late rejection due to noncompliance. Therefore, overall graft survival is 95%. The acute rejection rate at 6 and 12 months was 19% (no rejection occurred between months 6 and 12). Late rejection was uncommon, with only two further episodes beyond 12 months. Mean creatinine at 12 months was 144 micromol/L and mean estimated glomerular filtration rate (GFR) of 55 mL/min. Graft function was stable at 3 years with a mean creatinine of 142 micromol/L and mean estimated GFR 56 mL/min. During the study, five patients developed posttransplant diabetes mellitus (two cases beyond 12 months). Tissue-invasive cytomegalovirus disease and BK viral nephropathy each occurred in three patients, with all episodes in the first 12 months. Mean weight gain is 3.3 kg and mean blood pressure is 135/81 on an average of 1.5 antihypertensive agents. This steroid-avoidance regimen is associated with excellent medium-term patient and graft outcomes and a low incidence of side effects.

Late steroid withdrawal for renal transplant recipients on tacrolimus and MMF is safe.

INTRODUCTION: We conducted a study to assess the safety of staged, late steroid withdrawal in kidney or kidney/pancreas transplant recipients on steroids, tacrolimus, and mycophenolate mofetil (MMF). MATERIALS AND METHODS: We studied 50 patients including 33 recipients of cadaveric kidneys, eight living donor kidneys, and nine kidney-pancreas transplants. The mean time posttransplantation was 5.1 years (range 2.1 to 7.9 years). All patients were induced on prednisolone, tacrolimus, and MMF; steroids were withdrawn over 5 to 6 months. The rate of steroid reduction was altered in the face of typical steroid withdrawal symptoms (limb-girdle arthralgia/myalgia). RESULTS: No rejection episodes occurred during steroid withdrawal. No patient required transplant biopsy for graft dysfunction. Six patients failed steroid withdrawal: five due to arthralgia/myalgia and one due to recurrent pulmonary sarcoidosis. The unexplained rise in serum creatinine following steroid withdrawal described in several other steroid withdrawal studies was not observed in this patient cohort. The mean serum creatinine was 137 micromol/L with deltacreatinine -6.8 micromol/y per year prior to steroid cessation versus 132 micromol/L with deltacreatinine -5.9 micromol/y in the year post-steroid cessation. There were 14 patients with posttransplant diabetes mellitus in this cohort: eight on gliclazide and six on insulin. We observed a reduction in their daily insulin/gliclazide requirements from 52 units to 41 units, and 73 mg to 65 mg, respectively. Two patients became gliclazide-independent at the time of steroid cessation. CONCLUSIONS: Careful steroid withdrawal from a platform of tacrolimus and MMF is safe and not associated with a significant risk of rejection or graft dysfunction.

Five-year results of kidney transplantation under tacrolimus-based regimes: the persisting significance of vascular rejection.

BACKGROUND: Acute rejection has been the major risk factor for medium-term kidney graft loss because of chronic allograft nephropathy. We investigated whether the use of improved immunosuppression has altered the relationship between acute and chronic rejection by analyzing data from 245 renal transplant patients receiving Tacrolimus-based immunosuppression. RESULTS: Five-year graft survival (censored for death with functioning graft) was 88.8% with no significant difference between living and cadaveric kidney transplants. The only significant predictor of medium-term graft loss was acute vascular rejection. CONCLUSION: Under Tacrolimus-based immunosuppression, the occurrence of acute interstitial rejection, even when occurring late, repeatedly, or with failure of graft function to return to baseline, was not associated with chronic allograft nephropathy or medium-term graft loss. Vascular rejection remains the major immunological obstacle to long-term transplant success. Five-year overall survival rates with a functioning graft of 80% with 90% graft survival censored for death with function seem to be realistic and achievable goals.

Urinary retinol binding protein in Indo-Asian patients with idiopathic interstitial nephritis.

BACKGROUND: Idiopathic interstitial nephritis (IIN) is common in the UK Indo-Asian population. Lack of systemic involvement and unremarkable urinalysis on stick testing suggest that it may underlie some cases of end-stage renal failure of undetermined cause. If IIN is diagnosed early, prompt initiation of treatment can improve long-term outcome. AIMS: To investigate whether urinary retinol binding protein (RBP) is elevated more commonly than urinary albumin in IIN, and might be useful in the early detection of renal disease in Indo-Asian patients. DESIGN: Preliminary observational study METHODS: We measured urinary RBP and urinary albumin in 19 Indo-Asian patients in whom a renal biopsy had shown IIN, 10 of whom had already been treated with corticosteroids at the time of specimen collection. A further 28 Indo-Asian patients with glomerular disease, and six with normal light-microscopic renal biopsy, were assessed in parallel. RESULTS: Urinary RBP/creatinine ratio (RCR) was elevated in all 19 cases of IIN, compared to 12/19 in whom the albumin/creatinine ratio (ACR) was elevated. Elevated urinary RBP was thus significantly more common than albuminuria in this group (p<0.01). Twelve of the 19 cases also satisfied the criteria for tubular proteinuria. RCR was elevated to >30 times the upper limit of normal in 7/9 who had not previously received corticosteroids, of whom four had normal ACR; none had ACR >5 times the upper limit of normal. DISCUSSION: These data suggest that measurement of urinary RBP should be explored as an adjunct to albuminuria, if screening for renal disease in the Indo-Asian population is contemplated.

Dose optimization of mycophenolate mofetil when administered with a low dose of tacrolimus in cadaveric renal transplant recipients.

BACKGROUND: Supplementation of immunosuppressive therapy with mycophenolate mofetil (MMF) has been found to reduce the rate of acute rejection in renal transplantation. We report a dose-finding study for MMF when administered in combination with low-dose tacrolimus and corticosteroid prophylaxis in cadaveric renal transplant recipients. METHODS: Two hundred thirty-two patients at 16 centers were enrolled in this randomized, parallel-group study. The three treatment groups were tacrolimus and corticosteroids (MMF-0 group, n=82); tacrolimus, corticosteroids, and 1 g of MMF daily (MMF-1 g group, n=79); and tacrolimus, corticosteroids, and 2 g of MMF daily (MMF-2 g group, n=71). Study duration was 6 months, and patients were followed up for patient and graft survival for 12 months. RESULTS: At 6 months posttransplantation, daily doses of 1 g and 2 g of MMF were associated with significantly lower rates of acute rejection compared with tacrolimus alone. The Kaplan-Meier rates were 48.5%, 24.9%, and 22.9%, respectively, for the three treatment groups when acute rejection was determined by clinical criteria (P=0.007). At month 12, patient survival rates were 100%, 97.5%, and 97.2% and graft survival rates were 90.2%, 92.4%, and 93.0% for the MMF-0 group, MMF-1 g group, and the MMF-2 g group, respectively. Gastrointestinal adverse events and leukopenia were higher in the MMF groups, especially in the MMF-2 g group (P<0.05). CONCLUSIONS: Low-dose tacrolimus combined with a MMF dose of 1 g daily and corticosteroids provided an optimized efficacy and safety profile. A higher dose of MMF (2 g) was associated with greater toxicity without a significant improvement in efficacy.

Why is there so much end-stage renal failure of undetermined cause in UK Indo-Asians?

There is a high incidence of end-stage renal failure (ESRF) of undetermined cause in the Indo-Asian population of the UK. We studied patients presenting from the district of Brent and Harrow, which has a large Indo-Asian community, and whose renal services are largely provided by our centre. The diagnosis and ethnicity of patients starting renal replacement therapy and/or undergoing renal biopsy were collated. The incidences of ESRF, rates of renal biopsy and underlying diagnoses were calculated for Indo-Asians and Caucasians. Requirement for renal replacement therapy in Indo-Asians presenting to our centre from Brent and Harrow was 221/10(6)/year; no underlying diagnosis was identified in 77/10(6)/year. Renal biopsy rate in these patients was 456/10(6)/year, and the diagnostic categories significantly over-represented compared to Caucasians were: hypertension and ischaemia, focal segmental glomerulosclerosis (FSGS), idiopathic interstitial nephritis (IIN), diabetic nephropathy, minor glomerular abnormality, lupus nephritis and non-specific advanced chronic renal disease (p<0.001). The first three of these had a combined incidence of 135/10(6)/year in Indo-Asians and 31/10(6)/year in Caucasians. ESRF of undetermined cause is common in UK Indo-Asians, as is requirement for renal biopsy. Hypertension with ischaemia, FSGS and IIN are over-represented in the Indo-Asian population, and should be targeted for early diagnosis and treatment in this group.