KDIGO 2021 Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease

In nontransplant populations, effects of different antihypertensive drug classes vary. Relative effects in kidney transplant recipients are uncertain. We performed a systematic review including random effects meta-analysis of randomized controlled trials, using Cochrane Collaboration methodology. We identified 60 trials, enrolling 3802 recipients. Twenty-nine trials (2262 patients) compared calcium channel blockers (CCB) with placebo or no treatment, 10 trials (445 patients) compared angiotensin-converting enzyme inhibitors (ACEi) with placebo or no treatment, and seven studies (405 patients) compared CCB with ACEi. CCB compared with placebo or no treatment (plus additional agents in either arm as required) reduced graft loss (risk ratio [RR] 0.75, 95% confidence intervals [CI] 0.57-0.99) and improved glomerular filtration rate (GFR; mean difference [MD] 4.5 mL/min, 95% CI 2.2-6.7). Data on ACEi versus placebo or no treatment were inconclusive for GFR (MD -8.1 mL/min, 95% CI -18.6-2.4) and inconsistent for graft loss, precluding meta-analysis. In direct comparison with CCB, ACEi decreased GFR (MD 11.5 mL/min, 95% CI 7.2-15.8), proteinuria (MD 0.28 g/day, 95% CI 0.10-0.47), hemoglobin (MD 11.5 g/L, 95% CI 7.2-15.8), and increased hyperkalemia (RR 3.7, 95% CI 1.9-7.7). Graft loss data were inconclusive (RR 7.4, 95% CI 0.4-140). These data suggest that CCB may be preferred as first-line agents for hypertensive kidney transplant recipients.

Antihypertensives for Kidney Transplant Recipients: Systematic Review and Meta-Analysis of Randomized Controlled Trials

We compared the results of 44 renal transplants in children, of whom 24 were treated with CSA/ AZA and 20 with prednisone in combination with AZA and/or CSA. There were no differences in age distribution or mean ages at transplant between the two treatment groups. The CSA/AZA group had a longer follow-up (29 ± 33 vs 17 ± 18 months). At the last follow-up, five children in the CSA/ AZA and none in the prednisone group had lost their grafts. Serum creatinine increased in both groups from 0.7 ± 0.1 mg/dl and 0.9 ± 0.1 mg/dl at the end of the first month to 1.1 ± 0.2 mg/dl in the 36th month (CSA/AZA group) (P<0.0001) and to 1.5 ±0.6 mg/dl in the 18th month (prednisone group) (P < 0.05), respectively. Total cholesterol level was 189 ±52 mg/dl and 178 ± 60 mg/dl and LDL level was 117 ± 48 mg/dl and 115 ±51 mg/dl for the prednisone and CSA/AZA groups, respectively. HDL was greater in the CSA/AZA group (50± 10 vs 41 ± 10 mg/dl) (P < 0.03), and VLDL was greater in the prednisone group (31 ± 13 vs 22 ± 8 mg/dl) (P < 0.05). Serum triglyceride was greater in the prednisone group (174 ± 93 vs 112 ±50 mg/dl) (P < 0.03). The standard deviation score for height of the children in the prednisone group did not change ( 2.4 ± 1.4 vs -2.1 ± 1.4 SDS), whereas the SDS height score for the CSA/ AZA children increased from 3.1 ± 1. 7 to -2.6 ± 1.5, -1.9 ± 1.4 and -1.7 ± 1.4, at 12, 24 and 36 months, respectively (P < 0.001 ). CSA/ AZA is a good immunosuppressive regime for the first renal transplant in children, but only 75% tolerated AZA/CSA without same damage to their grafts.

Transplant International Official Journal of the European Society for Organ Transplantation

Aluminium chelation therapy in dialysis patients: evidence for inhibition of haemoglobin synthesis by low levels of aluminium.

Background In some nontransplant populations, effects of different antihypertensive drug classes vary. Relative effects in kidney transplant recipients are uncertain. Objectives To assess comparative effects of different classes of antihypertensive agents in kidney transplant recipients. Search strategy MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, conference proceedings and reference lists of identified studies were searched. Selection criteria Randomised controlled trials of any antihypertensive agent applied to kidney transplant recipients for at least two weeks were included. Data collection and analysis Data was extracted by two investigators independently. Study quality, transplant outcomes and other patient centred outcomes were assessed using random effects meta-analysis. Risk ratios (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes, both with 95% confidence intervals (CI) were calculated. Stratified analyses and meta-regression were used to investigate heterogeneity. Main results We identified 60 studies, enrolling 3802 recipients. Twenty-nine studies (2262 participants) compared calcium channel blockers (CCB) to placebo/no treatment, 10 studies (445 participants) compared angiotensin converting enzyme inhibitors (ACEi) to placebo/no treatment and seven studies (405 participants) compared CCB to ACEi. CCB compared to placebo/no treatment (plus additional agents in either arm as required) reduced graft loss (RR 0.75, 95% CI 0.57 to 0.99) and improved glomerular filtration rate (GFR), (MD, 4.45 mL/min, 95% CI 2.22 to 6.68). Data on ACEi versus placebo/no treatment were inconclusive for GFR (MD -8.07 mL/min, 95% CI -18.57 to 2.43), and variable for graft loss, precluding meta-analysis. In direct comparison with CCB, ACEi decreased GFR (MD -11.48 mL/min, 95% CI -5.75 to -7.21), proteinuria (MD -0.28 g/24 h, 95% CI -0.47 to -0.10), haemoglobin (MD -12.96 g/L, 95% CI -5.72 to -10.21) and increased hyperkalaemia (RR 3.74, 95% CI 1.89 to 7.43). Graft loss data were inconclusive (RR 7.37, 95% CI 0.39 to 140.35). Other drug comparisons were compared in small numbers of participants and studies. Authors' conclusions These data suggest that CCB may be preferred as first line agents for hypertensive kidney transplant recipients. ACEi have some detrimental effects in kidney transplant recipients. More high quality studies reporting patient centred outcomes are required.

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Antihypertensive treatment for kidney transplant recipients.

We have prospectively investigated the effect of desferrioxamine (DFO) administration (2 gi.v. after every haemodialysis session for 6 months) on the normocytic and normochromic anaemia of seven haemodialysis patients. None had either clinical or analytical data characteristic of chronic aluminium intoxication. At the end of DFO therapy, the haematocrit had increased from 20.5 +/- 2.7% to 30.4 +/- 7.7% (P less than 0.005), and the transfusional requirements decreased from 3.5 +/- 2.2 units (range 1-8 units) in the 6 months prior to DFO, to 0.7 +/- 0.9 units (range 0-2 units) during DFO administration (P less than 0.01). No transfusion was required during the second half of the DFO therapy period. Serum ferritin decreased from 105g +/- 532 nmol/l (2649 +/- 1331 ng/ml) to 507 +/- 403 nmol/l (1268 +/- 1008 ng/ml) (P less than 0.025). Two months after DFO withdrawal the haematocrit value fell significantly to 22.2 +/- 1.6% (P less than 0.01). DFO therapy was restarted in one patient at a lower dose (1 gi.v. after every haemodialysis session) and an increase of haematocrit from 23.8% to 40.2% was again observed after 3 months of treatment. The tolerance to DFO was excellent. We conclude that DFO therapy should be considered in haemodialysis patients with severe anaemia and increased blood transfusion requirements.

J Estenoz

Papers

Improvement of Anaemia With Desferrioxamine in Haemodialysis Patients

Calcium antagonist treatment of recipients minimizes early cyclosporine nephrotoxicity in renal transplantation: a prospective randomized trial.