Hypertension two years after renal transplantation: causes and consequences

The incidence of hypertension 2 years after renal transplantation and the possible causes of hypertension were studied retrospectively. A group of 93 patients treated with cyclosporin (CyA), azathioprine (Aza), and/or prednisolone (Pred) were compared to a group of 31 patients treated with Aza and Pred. There were more patients with hypertension in the CyA group (73%) than in the Aza group (58%). Hypertension before transplantation predisposed to hypertension after transplantation. After transplantation, hypertension was most common among patients with polycystic kidney disease (46%), chronic glomerulonephritis (67%), and diabetes (71%). The accumulated immunosuppressive medication (CyA/Pred) did not affect the occurrence of hypertension. Hypertensive patients had significantly poorer graft function than did normotensive patients (serum creatinine level 229 mumol/l vs 162 mumol/l, P < 0.01). The 10-year graft survival was markedly impaired in the group with hypertension (42% vs 65% for normotensives, P < 0.05). The 10-year patient survival was 59% vs 79% (P = NS). The study further confirms the frequent finding that hypertension has a negative effect on graft and patient survival rates.     

Cyclosporine trough concentrations in predicting allograft rejection and renal toxicity up to 12 months after renal transplantation

We recently identified a novel gene (PB39) (HGMW-approved symbol POV1) whose expression is up-regulated in human prostate cancer using tissue microdissection-based differential display analysis. In the present study we report the full-length sequencing of PB39 cDNA, genomic localization of the PB39 gene, and genomic sequence of the mouse homologue. The full-length human cDNA is 2317 nucleotides in length and contains an open reading frame of 559 amino acids which does not show homology with any reported human genes. The N-terminus contains charged amino acids and a helical loop pattern suggestive of an srp leader sequence for a secreted protein. Fluorescence in situ hybridization using PB39 cDNA as probe mapped the gene to chromosome 11p11.1-p11.2. Comparison of PB39 cDNA sequence with murine sequence available in the public database identified a region of previously sequenced mouse genomic DNA showing 67% amino acid sequence homology with human PB39. Based on alignment and comparison to the human cDNA the mouse genomic sequence suggests there are at least 14 exons in the mouse gene spread over approximately 100 kb of genomic sequence. Further analysis of PB39 expression in human tissues shows the presence of a unique splice variant mRNA that appears to be primarily associated with fetal tissues and tumors. Interestingly, the unique splice variant appears in prostatic intraepithelial neoplasia, a microscopic precursor lesion of prostate cancer. The current data support the hypothesis that PB39 plays a role in the development of human prostate cancer and will be useful in the analysis of the gene product in further human and murine studies.     

Outcome of plasma exchange therapy in thrombotic microangiopathy after renal transplantation

Thrombotic microangiopathy (TMA) in renal transplant recipients is commonly associated with calcineurin inhibitors (CNIs), though several factors such as vascular rejection, viral infections and other drugs may play a contributory role. We report a series of 29 patients with TMA, all of whom were on CNIs. Though plasma exchange (PEx) is widely used to treat TMA, therapeutic guidelines are not well defined. All our patients were treated with PEx and discontinuation of CNIs. Thrombotic microangiopathy was diagnosed at a median of 7 days post-transplant. The mean decrease in Hgb and platelets during TMA was 66% and 64%, respectively, and peak serum creatinine during TMA was 7.4 +/- 2.9 mg%. Mean duration of PEx therapy was 8.5 (range 5-23) days. Recovery of platelet count to 150K/mcL and Hgb to 8-10 g/dL were used as endpoints for PEx. Twenty-three/29 (80%) patients recovered graft function after PEx. Twenty/23 (87%) patients who recovered were placed back on CNl. Nineteen/20 (95%) patients tolerated reinstitution of CNl without recurrence of TMA. In post-transplant TMA, PEx was associated with a graft salvage rate of 80%, reversal of hematological changes can be used as the endpoint for PEx therapy and CNl can be reintroduced without risk of recurrence in the majority of patients.     

The renal sympathetic system and juxtaglomerular cells in experimental renovascular hypertension

Marked reduction of the monoaminergic nerve fluorescence and catecholamine tissue content were demonstrated in the ischemic kidney of rats made hypertensive by unilateral renal artery stenosis (two-kidney Goldblatt hypertension). The nonischemic kidney showed a normal degree of fluorescence and catecholamine content. The electron microscope failed to demonstrate recognizable nerves around most of the glomerular arterioles of the ischemic kidney, whereas a normal rich innervation was observed in the nonischemic side. The juxtaglomerular index and renal renin content were elevated in the ischemic kidney and markedly reduced in the nonischemic kidney. Juxtaglomerular cells were present in the glomerular mesangium and ultrastructurally showed changes consistent with increased renin synthesis. The extent of disruption of the sympathetic system in renal hypertension might play a role in the degree of hypersecretory response of the juxtaglomerular cells to renal artery constriction.     

Management of moderate to severe hypertension and proteinuria by nifedipine retard and perindopril after renal transplantation

The following analysis describes selected aspects of Saxonian social and medical care for people in need of help and elderly, via "community social service units". Almost 16% of people are older than 65 years in Saxonia, whereas the number of women is twice the number of men. To secure the social and medical care "community social service units" were founded partly from former municipal nursing stations of the former GDR and partly from newly founded institutions. Basic and medical care is an essential part of the supply in "community social service units". To approximate an all-embracing social and medical care, so-called "other tasks" complete the general service from a qualitative point of view.     

Blood pressure independent effects of nitrendipine on cardiac structure in patients after renal transplantation

Left ventricular hypertrophy is well established as a blood pressure independent cardiovascular risk factor in patients on renal replacement therapy. The effects of antihypertensive treatment on myocardial structure and function in renal transplant recipients have been so far only rarely investigated. In a double-blind, placebo-controlled study patients were randomized to the calcium channel blocker nitrendipine or placebo if the transplanted kidney had developed a stable phase. Normotensive patients received nitrendipine 2 x 5 mg daily or placebo, hypertensive patients received 2 x 10 mg up to 2 x 20 mg nitrendipine daily or placebo. To achieve adequate blood pressure control, all patients with still elevated blood pressure on study medication received antihypertensive drugs other than calcium channels blockers. Ambulatory blood pressure recording and 2D-guided M-mode echocardiography were performed at baseline and upon completion of the study. In addition, laboratory workup (including serum creatinine and lipids) was done, and serum aldosterone, plasma renin activity, plasma angiotensin II and blood glucose levels were measured in all patients at baseline and after at least 12 months of therapy. Ambulatory blood pressure was almost identical between both groups at study baseline and follow-up. In renal transplant patients on nitrendipine, posterior wall thickness (-0.10 +/- 1.77 mm) and septal wall thickness (-0.83 +/- 2.23 mm) did not change significantly from baseline. In contrast, posterior wall thickness (0.71 +/- 0.92 mm, P < 0.01) and septal wall thickness (0.97 +/- 2.20 mm, P < 0.05) increased in patients on placebo, which differed from the observed changes on nitrendipine (ANOVA: P = 0.093 and P = 0.048, respectively). Relative wall thickness, a parameter for concentric left ventricular hypertrophy, became numerically smaller on nitrendipine therapy from 0.46 +/- 0.07 to 0.44 +/- 0.09 (-0.02 +/- 0.09, NS) but increased from 0.42 +/- 0.08 to 0.48 +/- 0.08 in the placebo arm (+0.04 +/- 0.08, P < 0.02), which was also significant between the two groups (ANOVA: P = 0.036). Endocrine parameters, lipids and blood glucose were not different between the two groups. We conclude from these data that the calcium channel blocker nitrendipine exerted beneficial effects on cardiac structure in patients after renal transplantation independent of blood pressure.     

Centrally acting sympathetic inhibitors for therapy of patients with hypertension

The blood pressure is maintained by the tonic vasomotor activity of efferent sympathetic neurons which are tonically regulated by the rostral ventrolateral medulla (RVLM) in the brain. The alpha 2-adrenoceptor agonist such as clonidine, guanabenz and guanfacine, acts on RVLM to decrease sympathetic neuron activity and lower blood pressure. Drug such as alpha-methyldopa, through its metabolite alpha-methylnoradrenaline, acts like clonidine as an alpha 2-adrenoceptor agonist in the brain. Clonidine and allied drugs except for alpha-methyldopa also bind to imidazoline receptors, which is believed to mediate the hypotensive action. The centrally acting antihypertensive drugs are used for treatment of moderate to severe forms of hypertension and are effective in patients with renal failure. The treatment with these drugs induces central nervous system side effect of sedation and drowsiness, which limits the clinical usefulness and are believed to be mediated by central alpha 2-adrenoceptors. The new imidazoline compounds, rilmenidine and moxonidine, which selectively act on imidazoline receptors, may be a useful antihypertensive drug without such central side effects.     

Biopsy-induced tricuspid regurgitation after cardiac transplantation

Transvenous endomyocardial biopsy is now well-established as the gold standard for evaluation of possible rejection episodes after cardiac transplantation. From 1985 to August 1992, 1990 patients have undergone 193 cardiac transplantations at Barnes Hospital. One hundred eighty-three patients survived their initial hospitalization and serve as the study group. Their records were reviewed for the purposes of identifying those with tricuspid regurgitation as a complication of right ventricular endomyocardial biopsy. These patients have undergone a total of 2,960 biopsies for an average of 16.2 biopsies per patient. Over a mean follow-up period of 4.22 years, all patients have been evaluated with standard two-dimensional echocardiograms. Mild to moderate tricuspid regurgitation was very common, but was thought to be biopsy-induced only if severe and accompanied by flail components of the tricuspid valve. Twelve patients were identified with this entity at our institution. Of these, 5 had no symptoms and were receiving no diuretics, 3 had mild symptoms consisting of lower extremity edema and continued to receive diuretics, 2 had moderate symptoms, and 2 had right heart failure and anasarca refractory to medical therapy. Both of the severely affected patients subsequently required tricuspid valve replacement. We conclude that the tricuspid valve apparatus is at significant risk of injury during endomyocardial biopsy, that most patients will be minimally symptomatic due to tricuspid regurgitation when this injury occurs, and that when the injury is accompanied by severe symptoms, the likelihood of improvement with medical therapy is small.     

Coronary artery fistula after cardiac transplantation

A cardiac transplant recipient with multiple coronary artery fistulae draining into the right ventricle is described. These fistulae presumably resulted from repeated endomyocardial biopsies. The diagnosis of coronary artery fistulae was made at the annual coronary arteriography. The magnitude of the shunt remained small over eight years of follow-up.