It Takes Time After Bilateral Nephrectomy for Better Control of Resistant Hypertension in Renal Transplant Patients

Severe resistant hypertension in end-stage renal disease patients has traditionally been an indication for bilateral nephrectomy (BN) before kidney transplantation. Nevertheless the influence of BN on successful control of hypertension has not been well documented. We sought to clarify the effect of BN on blood pressure patterns and control in renal transplant patients.

Materials and Methods

We retrospectively reviewed 28 patients who underwent BN between November 2003 and May 2009 before or after kidney transplantation. Nineteen of them were under treatment with 4 or 5 antihypertensives according to the international guide lines; they had BN for resistant hypertension. They were considered as group 1 (G1). Nine patients operated for indications other than resistant hypertension; they constitute group 2 (G2) and considered as a control group. All patients received triple immunosuppresion according to our local protocol. BN was done either before, simultaneously or after transplantation. Antihypertensives were recorded before and after BN. We evaluated our patients at 3 months, 1 year, and 3 years. Acute rejection episodes and calcinurein nephrotoxicity were reported.

Results

In G1, the mean age was 30.2 years (range, 10-62). In G2, the mean age was 33.6 years (range, 11-61). Before BN, G1 patients used antihypertensive drugs (3.6 ± 1.05 drugs per day; mean ± SD), which was significantly higher than in G2 patients (2.0 ± 1.65 drugs per day; P = .02). Three months after BN, G1 patients used 2.6 + 0.9 drugs per day, with gradual reduction in number of antihypertensives to 1.4 ± 1.3 drugs per day at 3 years (P = .008). In G2, there was reduction in antihypertensive drug number per day, which was insignificant during the follow-up period. No difference was noted between G1 and G2 drug administered after BN. We conclude that BN is effective to help blood pressure control, in resistant hypertension in renal transplant patients, but it starts to show up 3 months after surgery, and continues to work for a year and more.     

Effect of prophylactic ganciclovir on cytomegalovirus infection in renal transplant recipients

Cytomegalovirus (CMV) infection is the most frequent infectiouscomplication observed in renal transplant recipients and inducesa significant morbidity in these patients due to CMV diseaseitself and to associated renal dysfunction or opportunisticsuperinfection. In order to evaluate the effect of ganciclovirprophylaxis we conducted an open-label prospective randomizedstudy of ganciclovir administration in CMV seronegative recipientsof a renal allograft from CMV seropositive donors. Ganciclovir(5 mg/kg b.i.d./day for 14 days) was started on day 14 aftertransplantation. Thirty-two patients were included in this study(15 in the control group, 17 in the ganciclovir group). Therewas no significant difference between the two groups for age,immunosuppressive regimen, number of rejection, steroid pulses,and OKT3 treatments. Renal and patient outcomes were similarin both groups. The rate of CMV infection and CMV disease weresimilar in both groups (80% and 73.3% in the control group versus70.6% and 47.1% in the ganciclovir group; P=NS). Less severeCMV disease was observed in the ganciclovir group compared tocontrols. The delay between transplantation and CMV infectionwas significantly longer in the ganciclovir group compared tocontrol group (68.1±5.1 versus 44.0±5.2 days,P<0.005). Twelve control patients (80%) versus nine (53%)of the ganciclovir group required curative treatment with ganciclovirafter the diagnosis of CMV infection (NS). All the patientsrecovered from CMV disease and no significant side-effect wasobserved during ganciclovir administration. We conclude that prophylactic ganciclovir administration fromday 14 to day 28 after transplantation does not prevent CMVinfection in seronegative recipients of renal allograft fromseropositive donors but prolongs the incubation period. Longerprophylaxis by ganciclovir in these patients should be tested.     

Long-term cardiovascular effects of pre-transplant native kidney nephrectomy in children

Left ventricular (LV) hypertrophy (H) and hypertension are prevalent in children with end-stage renal disease (ESRD) and after renal transplantation. Severe hypertension prior to renal transplantation has traditionally been an indication for native kidney nephrectomy. The impact of nephrectomy on cardiovascular disease has not been well documented. We retrospectively evaluated echocardiographic and ambulatory blood pressure monitoring (ABPM) data in 67 young adults who had undergone transplantation in the pediatric age with a mean follow-up of 10.4 years. Unilateral or bilateral nephrectomies had been performed in 32 patients. The number of antihypertensive drugs used prior to transplantation was significantly higher in the nephrectomized groups. At follow-up the amount of antihypertensive medications was similar between groups and no significant differences were observed in mean arterial blood pressure (MAP) or LV mass index (LVMi). LVH was observed in 50% of non-nephrectomized patients, 45.4% of patients with unilateral nephrectomy, and 44.4% of patients without native kidneys (p = n.s.). In conclusion, unilateral or bilateral nephrectomies prior to transplantation do not appear to influence blood pressure control or the prevalence of LVH after renal transplantation. Longitudinal studies with repeated assessment of LVMi, before and after renal transplantation, are needed to assess the impact of residual activity of native kidneys on arterial blood pressure and cardiac structural changes, even in normotensive patients, to evaluate cardiovascular morbidity.     

A double-blind, randomized, placebo-controlled study of nifedipine on early renal allograft function

A double-blind, randomized, placebocontrolled study was conductedto determine the effect of nifedipine on early renal allograftfunction when added to a triple therapy immunosuppression regimecomprising low-dose cyclosporin (CsA), prednisolone and azathioprine.Fifty adult cadaveric renal allograft recipients were randomizedto placebo (group P n=17), nifedipine 10 mg preoperatively and20 mg b.d. postoperatively for 48 h, followed by matching placebofor 3 months (group NS n=16) or nifedipine 10 mg preoperativelyand 20 mg b.d. postoperatively for 3 months (group NL n=17).Donor and recipient exclusion criteria included recent calciumantagonist treatment. At 3 months after transplantation meanGFR adjusted for graft loss was significantly higher in groupNL than in NS (mean ± SD 61±28 versus 34 ±25 ml/min/1.73 m²; P<0.05), group P being intermediate (45± 34ml/min/1.73 m²). Similarly, effective renal bloodflow (ERBF) at 3 months was higher ingroup NL than in groupsP and NS (mean ± SD 351 ± 175 versus 216±166and 220±162 ml/min/ 1.73 m²; P<0.05). The differenceswere not significant by 6 months post-transplantation. Thisstudy suggests that oral nifedipine commenced preoperativelyand continued for 3 months following transplantation has beneficialeffects on early renal allograft function whenincorporated aspart of an immunotherapy regimen based on cyclosporin.     

Kidney transplantation decreases the tissue level of advanced glycosylation end-products

We have studied the effect of chronic renal failure (CRF) andkidney transplantation on advanced glycosylation end-products(AGE) measured as collagen-linked fluorescence (CLF) in theskin and peritoneum of non-diabetic patients. Of 34 patientswith CRF, 18 were studied before the commencement of peritonealdialysis (CRF group), and 16 were studied 5–31 weeks afterkidney transplantation (transplant group). The control groupconsisted of 24 patients with normal renal function. Skin CLFin the CRF group (20.9 ± 2.02 U/mg) was higher than inthe control (8.52±1.08 U/mg, P = 0.0001) and transplantgroups (10.7 ± 2.43 U/mg, P=0.003). Peritoneal CLF inthe CRF group (30.5 ± 5.64 U/mg) was higher than in thecontrol group (16.1 ±2.25 U/mg, P=0.031) but was notdifferent from the transplant group (19.4 ± 3.66 U/mg,P=0.11). Peritoneal CLF of control and transplant groups werenot different (P= 0.45). The results of this study suggest thatrestoration of renal function affects tissue AGE levels.     

Recombinant human erythropoietin corrects anaemia during the first weeks after renal transplantation: a randomized prospective study

BACKGROUND.: Studies on the effect of recombinant human erythropoietin (rHuEpo)on haematopoiesis in patients with kidney transplants, havebeen limited to progressive chronic graft failure, late aftertransplantation. In the present prospective randomized study,the efficacy of rHuEpo in the correction of anaemia during thefirst weeks after renal transplantation (RTP) was evaluated. METHODS.: Patients were allocated to either an Epo-(n=14) or a non-Epo-treatedgroup (n=15). Epo (150 U/kg.week s.c.) was started at a haematocrit(Hct) <30% and was increased at weekly intervals by 30 U/kg.week,as long as Hct remained <25%. RESULTS.: In the Epo group, Hct increased from a nadir of 22±4%2 weeks after RTP to 30±4% at week 4 and to 36±4%at week 6 (P<0.001 and P<0.0001 respectively vs week 2).Corresponding values in the non-Epo group were 25±6%,28±6% (P=NS) and 32±6% (P<0.05 vs week 2) (overallevolution Epo vs non-Epo: P=0.038 by variance analysis). Thedifferences in Hct between the Epo and non Epo group were evenmore marked in patients without major complications (varianceanalysis P=0.009). The Epotreated patients required fewer post-surgicalblood transfusions (0.005 vs 0.014/days follow-up, P<0.05),in spite of greater post-surgical blood losses, especially atday 1 (P<0.05) and the presence of more major complications(7 vs 4) and a higher number of ganciclo vir-treated patients(4 vs 0; P<0.05). The maximum Epo dose after RTP was >2xhigher than the one required before RTP (197.1±45.1 vs85.0±76.0 U/kg.week; P<0.05). CONCLUSIONS.: It is concluded that rHuEpo during the first weeks after RTPis of benefit in the correction of the Hct in the early post-surgicalperiod, in spite of relative Epo resistance.     

Pneumocystis carinii pneumonia in renal transplant recipients

In 1991 and 1992 Pneumocystis carinii pneu monia (PCP) was diagnosedin 28 renal transplant recipients. The incidence of PCP in ourrenal transplant centre was remarkably increased from 1.1% before1991 to 11.5% in 1991–1992. We compared 28 PCP patientswith a control group of 27 renal transplant recipients, matchedfor transplantation day and with out an episode of PCP. Themean age was significantly higher in the PCP group (50±13 versus 38±13 years). We observed no differences inbasic immunosuppres sive and rejection treatment nor in antibioticconsump tion, number of hospitalization days, and incidenceof CMV infection. In March 1993 we introduced PCP prophylaxis.More than 140 renal transplant recipients received co-trimoxazole,starting 1 day after trans plantation and continued for a periodof 4 months. To the time of writing no one in this group haddeveloped PCP.     

Hyperuricaemia in cyclosporin-treated patients: a GFR-related effect

BACKGROUND: Hyperuricaemia is a well known side-effect of cyclosporin A(CsA) treatment. The pathogenic mechanisms, however, remaincontroversial. There is no convincing evidence that hyperuricaemiais due to CsA-induced, impaired tubular handling of uric acid.The impact of diminished GFR in this particular context hasnever been investigated. METHODS: We prospectively studied plasma uric acid, inulin clearances,and fractional clearances of uric acid in two groups of CsA-treatedpatients (bone-marrow transplant patients, n=50; renal transplantpatients, n=32), and one healthy control group without CsA (livingrelated kidney donors, n=28). Bone-marrow transplant patientswere examined before transplantation and 6, 12, 18, 24 monthsafter transplantation, renal transplant patients 1 year aftertransplantation, and living related kidney donors before and1 year after unilateral nephrectomy. RESULTS: After 1 year of CsA treatment, hyperuricaemia was found in 36%of bone-marrow transplant patients and in 53% of renal transplantpatients. Thirty per cent of living related kidney donors wereborderline hyperuricaemic 1 year after unilateral nephrectomy.The fractional clearance of uric acid, measured serially inbone-marrow transplant patients did not change significantlyover time; it was, however, slightly higher during CsA treatmentthan after CsA withdrawal. Moreover, the bone-marrow transplantpatients' fractional clearance of uric acid was not statisticallydifferent from the renal transplant patients' and the livingrelated kidney donors' (values 1 year after transplantation/unilateralnephrectomy: bone-marrow transplant patients, 15.3±2.3%;renal transplant patients, 11.9±0.9%; living relatedkidney donors, 11.1±0.8%). The GFR at 1 year, measuredby inulin clearance, was identical in the CsA-treated groupsand slightly higher in the living related kidney donors (bone-marrowtransplant patients, 51±6 ml/min per 1.73 m² renal transplantpatients, 49±3 ml/min per 1.73 m² living related kidneydonors, 61±2 ml/min per 1.73 min²). CONCLUSIONS: There is no evidence for impaired tubular handling of uric acid,induced by a CsA-specific tubulotoxic effect. Hyperuricaemiain CsA-treated transplant patients can therefore be attributedto the cyclosporin associated decrease of GFR.     

Antihypertensive effect of beta blockade in renal transplant recipients with or without host kidneys

Host kidneys may contribute considerably to hypertension after renal transplantation. Their role in sustaining hypertension is more prominent if glomerulonephritis (GN) than if interstitial nephritis (IN) is the original renal disease. We compared the antihypertensive effect of beta-blockade in IN (n = 10) and GN (n = 19) hypertensive renal transplant recipients with host kidneys in situ with those who had undergone bilateral nephrectomy (BN, n = 10). Pretreatment blood pressures were comparable in BN, IN, and GN patients, being 165 +/- 6/108 +/- 3, 172 +/- 5/104 +/- 3, and 161 +/- 3/104 +/- 1, mmHg, respectively. Blood pressure did not change on beta-blockade in BN patients, whereas it decreased significantly more (P less than 0.001) in GN than in IN patients, changes of mean arterial pressure being -107 +/- 1.0, -14.9 +/- 1.3, and -6.8 +/- 1.6%, respectively. This failure to respond to beta-blockade in patients without host kidneys may be related to low activity of the renin-angiotensin system or to functional denervation of the grafted kidney. Further investigations of this phenomenon may clarify the mechanism of antihypertensive action of beta-blockade as well as the nature of hypertension after renal transplantation.     

Effect of desmopressin substitution during organ procurement on early renal allograft function

BACKGROUND: As diabetes insipidus in brain-dead organ donors leads to hypovolaemia,hyponatraemia, and hypotension, desmopressin is recommendedfor treatment of diabetes insipidus. As its effect on earlyrenal allograft function remains unclear, we conducted a studyto evaluate the effect of desmopressin on renal-graft survival. METHODS: We report the results of a prospective study in 41 brain-deadorgan donors (mean age 45±12 years) with diabetes insipidus,who were treated either with adequate fluid substitution andbolus application of desmopressin (desmopressin group; n=22)or with volume substitution alone (control group; n=19). Donorsas well as recipients of both groups were well matched withrespect to age, sex, dopamine dosage, serum electrolytes, coldischaemic time, HLA match, number of prior transplantations,and current cytotoxic antibodies. Early renal allograft functionwas evaluated in 71 recipients (mean age 48±14 years)within 3 days after transplantation. RESULTS: Overall, primary non-function was observed in 26 (36.6%) of71 recipients. The rate of primary non-function was significantlyhigher in the desmopressin group compared to the control group(desmopressin group 48.6%; control group 23.5%; P=0.028). CONCLUSIONS: The use of desmopressin during organ procurement is associatedwith a higher rate of primary non-function of renal allografts.     

Regional versus general anesthesia for donor nephrectomy: effects on graft function

Various general and regional anesthesia methods are used successfully in living-donor kidney transplantation. This study compared kidney graft function after general versus combined spinal-epidural anesthesia for donor nephrectomy. The study groups included recipients who received grafts from donors who had undergone nephrectomy under general anesthesia (GA group; n=10), and recipients who received grafts from donors who had combined spinal-epidural anesthesia (CSE group, n=10). Standard continuous epidural anesthesia was administered during all transplantations. Graft function was assessed using scintigraphy and Doppler ultrasonography on days 3 and 7. Urine levels of microalbumin, creatinine, and creatinine clearance rate were measured/calculated in 24-hour urine samples collected on postoperative days 3 and 7. There were no differences on either day 3 or day 7 with respect to glomerular filtration rate, microalbuminuria, or creatinine clearance rate (P >.05 for all). There were also no differences between the groups with respect to other scintigraphic findings on day 3 or day 7 (P >.05 for all). Ultrasonography on day 7 showed significantly higher mean peak systolic flow in the main renal artery in the CSE group than in the GA group (P=.035). The results suggest that GA and CSE for donor nephrectomy have similar effects on kidney graft function in recipients.     

Hypothyroidism retards progressive glomerulosclerosis in the rat by a reduction in food intake

Hypothyroidism diminishes proteinuria and prolongs survivalin several immune models of progressive renal failure. In thewell-characterized non-immune model of 5/6 nephrectomy we studiedthe effects of thyroidectomy (Tx) on the development of proteinuriaand glomerulosclerosis (GS). Hypothyroidism was confirmed bylower values of thyroxine in Tx rats compared to sham Tx ratsat 9 weeks (12.6±6.7 nmol/l Tx versus 37.7±10.8nmol/l sham Tx) and 12 weeks after operation (7.2±4.9nmol/1 Tx versus 14.4±4.1 nmol/l sham Tx). Tx resultedin a reduction in mean arterial blood pressure and proteinuriaand a lower incidence of GS (4.2±3.1% Tx versus 17.1±10.0%sham Tx) 12 weeks after nephrectomy, along with a decrease infood intake (104±13 g/week Tx versus 138±10 g/weeksham Tx). In the same experiment a third group of sham Tx ratswas pair fed to the Tx rats, resulting in values similar tothose of Tx rats for proteinuria and the incidence of GS (6.0±4.9%pair fed sham Tx). Thyroxine levels at 9 and 12 weeks were comparableto those in sham Tx rats fed ad libitum. No association wasfound between the incidence of GS and glomerular volume. Studiesof the inulin clearance in a second set of experiments showedthat glomerular filtration rate and renal plasma flow are lowerin hypothyroid rats compared to sham Tx rats. We conclude that hypothyroidism has a renal protective effectdue to a decrease in food intake resulting in alterations inrenal haemodynamics.     

Influence of blood volume on the blood pressure of predialysis and peritoneal dialysis patients treated with erythropoietin

Twenty-seven patients with renal failure (16 on CAPD and 11predialysis) were treated with erythropoietin. At 12 weeks,the mean haemoglobin concentration (±SEM) in the CAPDpatients had increased from 7.07 ± 0.20 to 10.88 ±0.45 g/dl (two-tailed paired t test, P<0.0001) and in thepredialysis patients from 6.90 ±0.35 to 10.05 ±0.47 g/dl (P< 0.0001). Predialysis patients were taking moreantihypertensive medication at baseline. No increase was requiredin either group after erythropoietin; there was no change inblood pressure in the CAPD patients, though in the predialysispatients the systolic blood pressure rose slightly from 132to 146 mmHg (P=0.029) and the mean blood pressure from 95 to103 mmHg (P=0.028). In 12 patients (6 on CAPD and 6 predialysis) the red cell volume,plasma volume, and total blood volume were measured before andafter treatment. In the CAPD patients there was a marked expansionof the red cell volume from 912±127 to 1471±222ml (P=0.004) and a concomitant contraction of the plasma volumefrom 3932 ±250 to 3178 ±326 ml (P=0.005), leavingthe blood volume unchanged from 4843 ± 352 to 4649 ±503ml. Predialysis patients had a similar expansion of the redcell volume from 733 ± 59 to 1304± 161 ml (P=0.017)but no contraction of the plasma volume (from 3417 ±354to 3314 ±260 ml), so that the blood volume tended toexpand from 4149 ±347 to 4618 ±414 ml (P= 0.053).The mean contraction of the plasma volume in the predialysisgroup was trivial (– 102 ±214 ml), whereas in theCAPD group it was large (–754 ±158 ml, P=0.034,two-tailed unpaired t test). Thereby the predialysis group experiencedan expansion of the total blood volume of 469±186ml,whereas the CAPD group experienced a contraction of the bloodvolume of –195±189 ml(P=0.031). We conclude that (a) increased blood volume may contribute tothe exacerbation of hypertension induced by erythropoietin therapy;(b) gradual reduction of plasma volume, aiming for a stabletotal blood volume, is an important strategy for the preventionand control of erythropoietin-induced hypertension; (c) as reductionof plasma volume may be more problematic in predialysis patients,adequate blood pressure control may consequently be slightlymore difficult, placing more reliance on antihypertensive medication.     

Elevated plasminogen activator inhibitor levels in cyclosporin-treated renal allograft recipients

Atherosclerosis and thrombosis, two major causes of morbidityand mortality in renal transplant recipients, share the sameclinical risk factors including decreased fibrinolysis and lipiddisturbances. In a crosssectional study we have determined parametersof fibrinolysis in control subjects (n=23) and stable renalallograft recipients without cyclosporin CsA (n=10) and withCsA (n=87) in their immunosuppressive treatment. In CsA-treatedpatients, tissue-type plasminogen activator was moderately increasedcompared to patients without CsA (8.4±3.3 vs 5.5±2.8ng/ml). The plasminogen activator inhibitor (PAI) activity inplasma was clearly increased in CsA-treated patients: 14.5±8.8vs 7.2±3.2 in normal controls and 8.5±2.4 AU/mlin patients without CsA. Total cholesterol and LDL cholesterollevels were higher in CsA-treated patients (256±62 and169±60 mg/dl) than in patients without CsA (209±45and 136±44 mg/dl). The two groups did not differ in HDLcholesterol, triglycerides, and lipoprotein(a). Hypercholesterolaemia,obesity, and steroid-induced diabetes could be identified asrisk factors for elevated plasma PAI activity in CsA-treatedpatients. Hypofibrinolysis induced by elevated PAI levels andincreased LDL cholesterol may contribute to the increased thrombogenicityand accelerated atherosclerosis observed in cyclosporin-treatedpatients.     

Acute Responses of Parathyroid Hormone and 1,25 Dihydroxyvitamin D3 to Unilateral Nephrectomy in Healthy Donors

Plasma immunoreactive parathyroid hormone (iPTH), 1,25(OH)₂D3calcium and phosphate and urinary creatinine, calcium and phosphatewere measured before and following unilateral nephrectomy insix kidney donors. Unexpectedly, plasma calcium rose, from 2.27±0.02mmol/l (mean±SEM) to 2.41±0.03 mmol/l on day 7and to 2.37±0.02 mmol/l on day 30 (P<0.02). A parallelrise in iPTH occurred, from 0.61±0.16 ng/ml initially,to 1.83±0.54 ng/ml on day 7 (P<0.05) and to 1.18±0.18on day 30 (P<0.01). The ratio of maximal tubular reabsorptionof phosphate to GFR (TmP/GFR) fell by day 2 (P<0.001), remainingreduced on day 30 (P<0.05). The significance of elevated iPTH in renal insufficiency wasfurther assessed by determining the time course of the disappearanceof iPTH after parathyroidectomy in three haemodialysis subjects.Fifty per cent baseline iPTH level occurred after an averageof 104.7 min, suggesting that the assay did not predominantlyrecognize C-terminal PTH fragments. By day 2, plasma 1,25(OH)₂D3had fallen from 34.3±4.5 pg/ml to 22.8±3.8 pg/ml(P<0.001), but by day 4 had regained its pre-nephrectomyvalue. Our results suggest that hypocalcaemia may not be thesole stimulus to parathyroid hormone secretion. It is speculatedthat reduction in circulating 1,25(OH)₂D3 may be involved.     

Laparoscopic versus open bilateral nephrectomy in transplant recipients with medication-resistant hypertension: final results of a multicenter study with 15 years of follow-up

Background

The objective of this study was to evaluate the outcomes of laparoscopic bilateral nephrectomy (LBN) compared with open bilateral nephrectomy (OBN) in transplant recipients with medication-resistant hypertension.

Material and Methods

Between 1994 and 2009, 66 renal transplant recipients underwent LBN due to poorly controlled hypertension. We compared them with 44 previous patients who underwent OBN.

Results

The mean operative times for LBN and OBN were 195.4 ± 60.1 minutes and 145.7 ± 30.2 minutes, respectively (P = .013). The mean hospital stays were 4.2 ± 2.1 in the LBN versus 10.3 ± 3.9 days in the OBN groups; the mean complication rates were 9.1% versus 18.2%, respectively. At follow-up, the blood pressure (mean value 130/90 mm Hg) in 45 patients (68.2%) among the LBN group was well controlled without the need for antihypertensive medications. In 19 patients (28.8%) significantly fewer antihypertensive drugs (1 or 2) were needed compared with the preoperative status. The remaining 2 patients (3%), both of whom had returned to hemodialysis due to chronic transplant rejection, remained on a combination of 3 or more antihypertensive drugs. Among the open surgery group, 23 subjects (52.3%) showed significantly decreased arterial blood pressure without needing medical therapy; 18 patients (40.9%) required 1 or 2 drugs and the remaining 3 (6.8%) were on a combination of 3 or more antihypertensives. The last cohort had returned to hemodialysis due to chronic transplant rejection.

Conclusions

LBN showed a higher efficacy than open surgery to treat medication-resistant hypertension after renal transplantation, reducing the postoperative trauma and the morbidity rate in high-risk transplant recipients.     

Reduction of Blood Pressure Retards the Progression of Chronic Renal Failure in Man

The effect of blood pressure reduction on the progression rateof chronic renal failure (CRF) was studied in 28 patients withCRF of diverse aetiology entering a prospective study (observationtime 7–24 months, mean 16 months). Endogenous creatinineclearance was 12–66 ml/mm (mean 30±3 ml/mm). Weaimed to keep the blood pressure below 160/90 mmlHg. Dietaryprotein was not restricted. The progression rate of CRF wasassessed from the regression coefficients of the regressionsof creatinine clearance and the inverse of s-creatinine, respectively,on time. Progression rate and the means of all recordings ofmean arterial blood pressure (MAP) and urinary protein excretion,respectively, in each patient during the prospective phase werecompared with retro spective data from the proceeding period(observation time 4–25 months, mean 19 months). The patientsreceived various combinations of antihypertensive drugs includingdiuretics, beta-blockers and vasodilatory drugs. In 19 patientsMAP decreased from 109±2 to 102±2 mmHg (groupI), whereas MAP increased from 105±2 to l08±2mmHgin nine patients (group II). In group I proteinuria was significantlylower (P<0.05) and the progression of CRF was approximately50% slower (P.<0.01) in the prospective phase than in theretrospective phase; no changes were observed in group II. Calculatedfor all patients, significant correlations were observed betweenthe change in MAP and the change in progression rate and proteinexcretion, respectively. These results indicate that loweringof blood pressure results in decreased proteinuria and retardationof the progression of CRF irrespective of the aetiology.     

Chronic effects of endothelin-3 on blood pressure and renal haemodynamics in rats

BACKGROUND.: Renal vasoconstriction and systemic hypertension are well-knowneffects of bolus or short-term endothelin administration. However,the role of endothelin as a circulating hormone remains largelyunknown. METHODS.: The present study explores the effects of endothelin-3 (ET-3)on renal haemodynamics and systemic blood pressure during a3-h and a 3-day intravenous infusion in rats. Male Sprague-Dawley(SD) rats were infused with vehicle (group 1) or ET-3 (group2, 10 ng/kg per min; group 3, 50 ng/kg per min) delivered viaosmotic minipumps into the right jugular vein for 3 days. Onday 3 after pump implantation, rats were anaesthetized withInactin and surgically prepared for assessment of mean arterialblood pressure (MABP), renal plasma flow (RPF), glomerular filtrationrate (GFR), and renal vascular resistance (RVR). The same parameterswere assessed during a 3-h ET-3 infusion study in SD rats (group4, vehicle; group 5, ET-3, 10 ng/kg per min; group 6, ET-3,50 ng/kg per min). RESULTS.: In 3-day infused rats, ET-3 induced a significant decrease inRPF (–22±7% and –26±8% for group 2and group 3 respectively, P<0.05 vs group 1) and an increasein RVR (+40±11% for groups 2 and 3; P<0.05 vs group1); 50 ng/kg per min ET-3 significantly decreased GFR (–17%,P<0.05 vs group 1). MABP was not significantly affected byendothelin infusion. In acute infusion studies a decrease ofthe same magnitude was seen for the renal haemodynamics values.50 ng/kg per min ET-3 increased MABP; a systemic effect thatdisappeared after the 3-day infusion. CONCLUSIONS.: This study suggests that intravenously administered ET-3 inthe rat has only a transient effect on systemic blood pressure,whereas it induces alterations in renal haemodynamics afterboth acute and chronic perfusions.     

DOSE REQUIREMENTS AND PLASMA CONCENTRATIONS OF PIPECURONIUM DURING BILATERAL RENAL EXCLUSION AND ORTHOTOPIC LIVER TRANSPLANTATION IN PIGS

We have studied five pigs undergoing bilateral clamping of therenal pedicles, seven pigs undergoing orthotopic liver transplantationand three control animals without surgery in order to examinethe roles of the kidney and liver in the plasma clearance ofpipecuronium. An i.v. infusion of pipecuronium was controlledto maintain a constant 90–95 % twitch depression throughoutthe investigation. The right sciatic nerve was stimulated continuouslywith supra-maximal stimuli at 0.1 Hz and the force of the correspondingevoked isometric muscle contraction was recorded continuously.Control pigs needed an infusion rate of pipecuronium 8–10.7µg kg^–1 min^–1. In the renal group, it wasnecessary to reduce the infusion rate of pipecuronium by about25% after clamping both renal vascular pedicles (P < 0.05compared with controls); in pigs undergoing liver transplantation,it was necessary to reduce the rate by approximately 80% afterclamping hepatic vessels (P < 0.05 compared with controlsand from the period after clamping of renal vessels). Afterhepatic recirculation, the infusion rate of pipecuronium wasincreased progressively to a rate which corresponded to 50%of baseline values (P < 0.05 compared with the anhepaticphase and from controls). Plasma concentrations of pipecuroniumwere comparable in the three animal groups and did not changesignificantly during the study. These data suggest that theliver plays a more important role than the kidney in the plasmaclearance of pipecuronium in pigs.     

Bone loss after kidney transplantation: a longitudinal study in 115 graft recipients

BACKGROUND.: Bone loss is an important problem in renal transplant recipientsimmediately after surgery. No data are available about the boneloss beyond the first post-transplantation year. METHODS.: In a longitudinal, uncontrolled observational study bone mineraldensity (BMD) was measured by dual X-ray absorptiometry in 115renal graft recipients starting at different times after transplantation(0–20 years after transplantation) with a follow-up timeof 12 months. RESULTS.: A total of 56 patients showed a reduction of BMD during theobservation period. Bone loss depended on the time after transplantation.Mean reduction of BMD at lumbar spine was 7±10%, 1±9%during the first and second postoperative year. Beyond the thirdyear bone mineral density did not change or even increased slightly(0±4% during 3–5th year, 1±6% during 6–10thyear and 2±4% during 11–20th year after transplantation).Decrease of BMD correlated with a higher mean daily prednisonedosage (P<0.001), a higher cumulative prednisone dose (P<0.01),a more frequent and more steroid-resistant rejection (P<0.001)and a higher initial parathyroid hormone level (P<0.001).Patients with 25-OH-cholecalciferol therapy (P<0.05) or morephysical activity (P<0.05) had a smaller bone loss. CONCLUSIONS.: Reduction of BMD after transplantation is highest within thefirst post-transplant year. The effects of acute graft rejection,prednisone dosage and initial parathyroid hormone level arepredominant among the multiple factors associated with pronouncedbone loss.