[Comments on the guidelines (2018) of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH) on the management of arterial hypertension]. / Kommentar zu den Leitlinien (2018) der Europäischen Gesellschaft für Kardiologie (ESC) und der Europäischen Gesellschaft für Hypertonie (ESH) für das Management der arteriellen Hypertonie.

Arterial hypertension represents one of the most frequent chronic diseases that can lead to complications, such as stroke, dementia, heart attack, heart failure and renal failure. By 2025 the number of hypertensive patients will increase to approximately 1.6 billion people worldwide. The new guidelines of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH) on the management of arterial hypertension replace the guidelines of the ESC/ESH from 2013. The 2018 guidelines of the ESC/ESH were adopted by the German Cardiac Society and the German Hypertension League. In these comments national characteristics are worked out and the essential new aspects of the guidelines are critically discussed. These include, for example, the definition of hypertension, the importance of out of office blood pressure measurements, revised blood pressure targets, the modified algorithm for drug treatment and the relevance of device-based hypertension treatments. Important aspects for the management of hypertensive emergencies are also presented.

[Baroreceptor activation therapy for therapy-resistant hypertension: indications and patient selection : Recommendations of the BAT consensus group 2017]. / Barorezeptorakivierungstherapie bei therapierefraktärer Hypertonie: Indikation und Patientenselektion : Empfehlungen der BAT-Konsensusgruppe 2017.

Baroreceptor activation therapy (BAT) has been available for several years for treatment of therapy-refractory hypertension (trHTN). This procedure is currently being carried out in a limited number of centers in Germany, also with the aim of offering a high level of expertise through sufficient experience; however, a growing number of patients who are treated with BAT experience problems that treating physicians are confronted with in routine medical practice. In order to address these problems, a consensus conference was held with experts in the field of trHTN in November 2016, which summarizes the current evidence and experience as well as the problem areas in handling BAT patients.

Multidisciplinary Approach in the Treatment of Resistant Hypertension.

With its high prevalence and the eminent number of undetected or poorly controlled patients, the management of arterial hypertension is still a challenging task. Uncontrolled blood pressure is the major adjustable risk factor for cardiovascular end organ damage for coronary heart disease, heart failure, stroke, and renal disease. Patients with resistant hypertension often need a multidisciplinary approach in order to control their blood pressure sustainably. In cooperation with hypertension specialists, the underlying cause for therapy resistance should be evaluated. Pseudohypertension, white coat hypertension, and non-adherence need to be addressed. The medication can often be optimized and simplified. Reducing the number of pills per day can enhance the drug-adherence remarkably. The multidisciplinary evaluation of secondary causes of hypertension includes an endocrinological work-up, ruling out relevant sleeping disorders, and renal diagnostics. If there are no causative treatments possible and pharmacological and non-pharmacological measurements are not sufficient to control the blood pressure, one has to consider multidisciplinary approaches bringing nurses, pharmacists, dieticians, physiotherapists, social workers, psychologists, and community health workers onboard. Utilizing various strategies might improve medication management, patient follow-up, adherence, and self-management. Interventional therapy such as renal renervation, baroreflex activation therapy, or carotid body modulation is the final option that can be discussed with interventional active colleagues. However, large randomized controlled trials proving a benefit of these interventional therapies are still missing. The use of these still experimental approaches should be restricted to randomized controlled trials accordingly.

Predictors of Impaired Postpartum Renal Function in Women after Preeclampsia: Results of a Prospective Single Center Study.

Objective. The purpose of this prospective study was to investigate the predictive value of single prepartum findings combined with serum biomarkers sFlt-1 (soluble fms-like tyrosine kinase-1) and PlGF (placental growth factor) indicating severity of preeclampsia (PE) for occurrence and extent of impaired postpartum kidney function. Study Design. In this prospective, single center study 44 PE patients were compared to 39 healthy controls (similar in age and gestational age with singleton pregnancy) evaluated at time of delivery and at 6 months and 12 months postpartum. p values below 0.05 are considered statistically significant. Results. The majority of the PE patients had persistence of proteinuria (>120 mg/L after delivery) 6 months (p = 0.02) and 12 months postpartum (p < 0.0001) compared to controls. Also reduced GFR (glomerular filtration rate) persisted up to 6 months postpartum in PE patients compared to controls (p < 0.001). Prepartum sFlt-1 levels indeed correlated with impaired renal function parameters. Conclusion. A significant proportion of our PE patients had lower GFR levels and persistent proteinuria up to 12 months postpartum. Prepartum sFlt-1 is a trend-setting marker for impaired renal function postpartum, but it is not sufficient enough to predict renal impairment after PE. An evaluation of 24-month follow-up data is scheduled.

[Primay hyperaldosteronism--diagnostic and treatment]. / Primärer Hyperaldosteronismus--Diagnostik und Therapie.

Primary hyperaldosteronism (PHA) is characterized by an increased Aldosterone synthesis which is independent of the Renin-Angiotensin-Aldosterone-System (RAAS). The prevalence of PHA in patients who present in specialized hypertension centers is approx. 10 %. Besides patients with the classical symptoms known as "Conn-Trias" (hypertension, hypokalemia, metabolic alkalosis), the more frequent normokalemic patients with PHA also show a worse outcome compared to patients with essential hypertension. Identifying these patients is an important task in the evaluation of hypertension since targeted treatment options are available. Screening for PHA using the Aldosterone-Renin-Ratio (ARR) should be performed in patients with hypokalemic, severe or resistant hypertension. In addition, young patients with early onset of severe hypertension and/or positive family history should be screened. A positive screening result should be followed by a confirmatory test. The saline infusion test is the preferred clinical test for confirming a suspected PHA since it is accessible and time efficient. Other confirmatory tests are not used on a regular basis. After any confirmatory test, CT- or MRI-imaging and adrenal vein sampling (AVS) is used in order to differentiate between a unilateral adenoma, a bilateral hyperplasia or another cause of PHA. CT or MRI usually cannot discriminate smaller tumors form hyperplasia. Therefore AVS is used to detect lateralization of autonomous aldosterone production. Lateralization of aldosterone production indicates a unilateral adenoma. In these cases, laparoscopic adrenalectomy is the therapeutic option of choice with a hypertension cure rate of up to 60 %. If no lateralization is detectable, bilateral hyperplasia as the underlying cause of PHA is likely. Pharmacological inhibition of the mineralocorticoid receptor is the preferred treatment option in these cases. If Spironolactone is not well tolerated, Eplerenone and potassium-sparing diuretics should be prescribed. Often, however, in order to fully control hypertension, additional antihypertensive therapy is necessary.

[Treatment resistant hypertension. Value of a new treatment concept]. / Therapierefraktäre Hypertonie. Stellenwert neuer Therapiekonzepte.

Sympathetic overexpression can be found in a majority of hypertensive patients. Resistant arterial hypertension requires a targeted diagnostic procedure in order to exclude secondary causes of hypertension which can be treated specifically with established therapies. If secondary reasons are not identified, the antihypertensive medication is already optimal and lifestyle changes have been realized, but still the goal of antihypertensive therapy cannot be achieved, alternative invasive therapy strategies such as renal sympathetic denervation and baroreflex activation have been developed to achieve blood pressure control. These therapies are restricted to specialized centers which treat well-defined patients with therapy-resistant hypertension. Little long-term data concerning safety and efficacy are available for the two strategies. However, they should preferably be used as an ultima-ratio and add-on pathway to conservative procedures when established medication fails to achieve blood pressure control. To date, the effectiveness of the interventional antihypertensive therapies has only been shown on patients with systolic blood pressure over 160 mmHg and a mean oral medication of five drugs.

Comparison of the saline infusion test and the fludrocortisone suppression test for the diagnosis of primary aldosteronism.

For the diagnosis of primary aldosteronism (PA), confirmatory testing is mandatory and different function tests can be employed. There are, however, sparse data comparing the fludrocortisone suppression test (FST) and the saline infusion test (SIT). Patients with PA (n=90) or essential hypertension (n=65) were studied. They underwent one or the other test or both of them. Using the DPC Siemens aldosterone radioimmunoassay, we found that the SIT led to a stronger suppression of aldosterone than the FST. Post-test aldosterone-to-renin ratios (ARRs) and the percentage of suppression of aldosterone serum concentrations performed worse. The same results were observed in patients who underwent both FST and SIT. Some patients had divergent results in both tests. For the SIT, a lower cutoff value should be used than for the FST for the adequate identification of patients with unilateral PA. Long-term prospective studies are needed to address the question at what cutoff values patients benefit from subtype differentiation of PA. We discuss here possible explanations for divergent results obtained with both tests.

[Expert consensus statement on interventional renal sympathetic denervation for hypertension treatment]. / Interventionelle renale Sympathikusdenervation zur Behandlung der therapieresistenten Hypertonie.

This commentary summarizes the expert consensus and recommendations of the working group 'Herz und Niere' of the German Society of Cardiology (DGK), the German Society of Nephrology (DGfN) and the German Hypertension League (DHL) on renal denervation for antihypertensive treatment. Renal denervation is a new, interventional approach to selectively denervate renal afferent and efferent sympathetic fibers. Renal denervation has been demonstrated to reduce office systolic and diastolic blood pressure in patients with resistant hypertension, defined as systolic office blood pressure ≥ 160 mm Hg and ≥ 150 mm Hg in patients with diabetes type 2, which should currently be used as blood pressure thresholds for undergoing the procedure. Exclusion of secondary hypertension causes and optimized antihypertensive drug treatment is mandatory in every patient with resistant hypertension. In order to exclude pseudoresistance, 24-hour blood pressure measurements should be performed. Preserved renal function was an inclusion criterion in the Symplicity studies, therefore, renal denervation should be only considered in patients with a glomerular filtration rate > 45 ml/min. Adequate centre qualification in both, treatment of hypertension and interventional expertise are essential to ensure correct patient selection and procedural safety. Long-term follow-up after renal denervation and participation in the German Renal Denervation (GREAT) Registry are recommended to assess safety and efficacy after renal denervation over time.

PTH-receptors regulate norepinephrine release in human heart and kidney.

Recent data suggests that chronic renal failure and hyperparathyroidism are associated with sympathetic overactivity. Since peptide hormones are known to modulate norepinephrine (NE) release by activating prejunctional receptors, this study investigates whether parathyroid hormone fragment (1-34) (hPTH(1-34)) increases neuronal NE release in human heart and kidney. Using specific PTH-receptor agonists and antagonists, this study furthermore highlights functional differences between PTH1 and PTH2 receptors. Human atrial and renal tissues were incubated with [(3)H]-NE and superfused. Three electrical stimulations (5Hz, 1min) induced a stable [(3)H]-NE release which was taken as an index of endogenous NE release. RT-PCR with specific primers for PTH1- and PTH2-receptor was performed in heart and kidney. hPTH(1-34) (0.01-0.1µmol/L) and a stable analog of its second messenger cAMP (8-bromo-cAMP) increased [(3)H]-NE release in human atria. This facilitatory effect of PTH was also observed in human renal cortex. The PTH1-receptor antagonist (D-Trp(12), Tyr(34))-pTH-(7-34) (0.5µmol/L) abolished the effect of hPTH(1-34). This data was verified using isolated perfused mouse kidneys. Tuberoinfundibular peptide of 39 residues (TIP-39) (0.1nmol/L-0.1µmol/L) decreased [(3)H]-NE release in atria. PTH1- and PTH2-receptor expressions were demonstrated in human heart and kidney. Moreover, a splice variant of the PTH2-receptor was detected in human kidney. In conclusion, PTH is able to facilitate NE release in human atria and renal cortex by activation of PTH1-receptors. The highly increased PTH levels that can be observed in chronic renal failure might be one contributor for the elevated sympathetic nerve activity and the associated cardiovascular mortality in patients with end stage renal disease.

Chronic treatment with angiotensin-(1-7) improves renal endothelial dysfunction in apolipoproteinE-deficient mice.

BACKGROUND AND PURPOSE: ApolipoproteinE-deficient [apoE (-/-)] mice, a model of human atherosclerosis, develop endothelial dysfunction caused by decreased levels of nitric oxide (NO). The endogenous peptide, angiotensin-(1-7) [Ang-(1-7)], acting through its specific GPCR, the Mas receptor, has endothelium-dependent vasodilator properties. Here we have investigated if chronic treatment with Ang-(1-7) improved endothelial dysfunction in apoE (-/-) mice. EXPERIMENTAL APPROACH: ApoE (-/-) mice fed on a lipid-rich Western diet were divided into three groups and treated via osmotic minipumps with either saline, Ang-(1-7) (82 µg·kg(-1) ·h(-1) ) or the same dose of Ang-(1-7) together with D-Ala-Ang-(1-7) (125 µg·kg(-1) ·h(-1) ) for 6 weeks. Renal vascular function was assessed in isolated perfused kidneys. KEY RESULTS: Ang-(1-7)-treated apoE (-/-) mice showed improved renal endothelium-dependent vasorelaxation induced by carbachol and increased renal basal cGMP production, compared with untreated apoE (-/-) mice. Tempol, a reactive oxygen species (ROS) scavenger, improved endothelium-dependent vasorelaxation in kidneys of saline-treated apoE (-/-) mice whereas no effect was observed in Ang-(1-7)-treated mice. Chronic treatment with D-Ala-Ang-(1-7), a specific Mas receptor antagonist, abolished the beneficial effects of Ang-(1-7) on endothelium-dependent vasorelaxation. Renal endothelium-independent vasorelaxation showed no differences between treated and untreated mice. ROS production and expression levels of the NAD(P)H oxidase subunits gp91phox and p47phox were reduced in isolated preglomerular arterioles of Ang-(1-7)-treated mice, compared with untreated mice, whereas eNOS expression was increased. CONCLUSION AND IMPLICATIONS: Chronic infusion of Ang-(1-7) improved renal endothelial function via Mas receptors, in an experimental model of human cardiovascular disease, by increasing levels of endogenous NO.

Familial hyperaldosteronism I-III.

Primary aldosteronism is the most frequent cause of secondary hypertension. Three variants of familial hyperaldosteronism are known today. Early onset hypertension and severe target organ damage are hallmarks of the heritable forms. The underlying gene defect has already been identified in familial hyperaldosteronism type I. In type II and III research is ongoing. A highly variable phenotype often precludes the discovery of the familial appearance of these syndromes. Taking a sound family history is extremely important to discover the Mendelian pattern of inheritance. The identification of affected families is highly rewarding because all variants can potentially be cured or at least specifically treated. Testing the relatives of an index patient sometimes even allows preemptive treatment. However, the availability of specific treatment options necessitates a solid differentiation between the three syndromes to avoid unnecessary medical therapy or surgery.

Preprocurement pancreas allocation suitability score does not correlate with long-term pancreas graft survival.

BACKGROUND: Within recent years, more marginal donors have been offered to Eurotransplant. To help identify suitable pancreas donors, the Eurotransplant Pancreas Advisory Committee introduced a donor score system (P-PASS). Little is known about the influence of P-PASS on long-term pancreas graft survival. METHODS: From June 1994 to September 2009, we performed 405 pancreas transplantations. In a retrospective study we analyzed P-PASS in 318 cases. Pancreas grafts from donors with P-PASS < 17 (n = 146) analyzed for graft and patient survival as well as for surgical complications were compared with donors of a PASS > or = 17 (n = 172). The mean follow-up was 7.2 +/- 4.3 years. RESULTS: Recipient characteristics were comparable in both groups. Mean P-PASS was 16.7 +/- 2.7 for both groups: 14.3 +/- 1.5 for P-PASS < 17 and 18.8 +/- 1.6 for P-PASS > or = 17. Pancreas graft survival rates for 1, 5, and 10 years were 85%, 77%, and 73% among P-PASS < 17 and 81%, 73%, and 64% among P-PASS > or = 17 groups (P = .12). There were 12 (8.2%) cases of venous thrombosis in the <17 group and 22 (12.7%) in the > or =17 group (P < .05). The relaparotomy rate was significant higher (38.7% vs 28.7%) and duration of hospital treatment longer (40.2 vs 32 days) in the P-PASS > or = 17 group (P < .05). There was no significant difference in patient or kidney graft survival between groups. CONCLUSIONS: The data demonstrated that utilization of pancreas grafts from donors with a P-PASS > or = 17 resulted in good overall outcomes and could expand the organ donor pool. There was no correlation between P-PASS and long-term patient or graft outcome. Complications requiring relaparotomy were more frequent among patients after transplantation from donors with higher P-PASS.

En bloc retroperitoneal pancreas-kidney transplantation with duodenoduodenostomy using pediatric organs.

BACKGROUND: Given the shortage of organ donors, there is a critical need to use all available pancreas grafts for transplantation. In the Eurotransplant region, only 26% of all offered pancreas grafts were transplanted during 2007. Pediatric donors are rarely used in pancreas transplantation. METHODS: In this case report, we describe a retroperitoneal en bloc pancreas-kidney transplantation (SPK) with systemic venous anastomosis and duodenoduodenostomy using grafts from an 11-year-old child. The bloc was transplanted in a 42-year-old type I diabetic patient with end-stage renal disease. The proximal end of the aortic graft was closed. Arterial anastomosis was performed end-to-end between right internal iliac artery and the aortic graft because of severe atherosclerosis. Donor portal vein and donor renal vein were anastomosed separately end-to-side to recipient inferior vena cava. Exocrine drainage was carried out with a side-to-side duodenoduodenostomy. Both grafts were in the retroperitoneal position. RESULTS: The pancreas graft functioned immediately, the kidney graft resumed function at 7 days posttransplantation. Graft function was excellent over a follow-up of 18 months. The patient had no episodes of acute rejection or graft dysfunction, no severe infections, and no additional morbidity from the modified technique of retroperitoneal pancreas transplantation using duodenoduodenostomy. CONCLUSIONS: This case indicates that pediatric donors could be used more frequently in pancreas transplantation for adult recipients and could increase the organ donor pool. En bloc SPK is a feasible and safe technique. Further studies are required to confirm the benefits of a retroperitoneal SPK using duodenoduodenostomy.

Long-term results after simultaneous pancreas-kidney transplantation using donors aged 45 years or older.

UNLABELLED: With the shortage of organ donors, there is a critical need to use all available pancreas grafts for transplantation. METHODS: From June 1994 to December 2006 we performed 340 pancreas transplantations (317 simultaneous pancreas-kidney 5 pancreas only, 18 pancreas after kidney) including 69 (20%) transplantations from donors aged 45 years or older. Pancreas grafts from older donors were analyzed for graft and patient survival as well as surgical complications, compared with results from younger donors. RESULTS: Recipient characteristics were comparable in both groups. The older donor group mean age was 47.8 years (+/-2.1) versus 27.9 years (+/-10.3) for the younger group. Cumulative patient survival was 96% versus 98% after 1, 82% versus 91% after 5 and 82% versus 88% after 10 years with 1-5- and 10-year kidney graft survivals of 82%, 72%, 57% versus 93%, 83%, 73%, respectively. Pancreas transplant survival after 1, 5, and 10 years were 69%, 60%, 45% in older and 88%, 76%, and 72% in younger donor cohorts. There were 14 (20%) cases of venous thrombosis in the older group and 25 (9%) in the younger group (P = .012). CONCLUSION: Our results demonstrated that utilization of pancreas grafts from donors over 45 years resulted in acceptable outcomes after simultaneous pancreas-kidney transplant and could expand the donor pool. Among the older donor group, patient survival was slightly lower than the younger group, whereas pancreas graft function was significantly inferior (P < .01). Since venous thrombosis was the main reason for pancreas graft loss in older group, anticoagulation is essential.

[Comparison of adrenal imaging and selective adrenal vein sampling in primary hyperaldosteronism]. / Vergleich von Bildgebung und seitengetrennter Nebennierenvenen-Blutentnahme zur Differentialdiagnose bei primärem Hyperaldosteronismus.

BACKGROUND AND OBJECTIVES: There is a high prevalence for primary hyperaldosteronism (PHA) in hypertensive patients. This retrospective study was performed to determine the role of adrenal scanning and adrenal vein sampling (AVS) in distinguishing unilateral autonomous adenoma from idiopathic bilateral hyperplasia (IHA). METHODS: 93 patients, admitted to the radiology department for AVS between 1996 and 2004, were enrolled. 44 had a diagnosis of PHA, 22 or whom had an adenoma and 22 had IHA. RESULTS: 17 of the 22 patients with adenoma and 15 with IHA had an aldosterone-renin ratio > 50. Adrenal CT or MR scanning was performed in 73 patients. Sensitivity and specificity were 56 % and 60 %, respectively, for CT and 57% and 67% for MR. In 87 patients AVS provided values for aldosterone (A) and cortisol (C) from the adrenal veins and vena cava inferior (VCI). Successful sampling (C-adrenal vein/C-VCI > 1.1) was achieved from 55 % of the right and from 92 % of the left adrenal veins. When AVS was successful on both sides, localizing adenoma was possible using A/C (site of adenoma) vs. A/C (contralateral) at a cut-off point > 3 (sensitivity 85 %, specifity 88 %). In patients with adenoma, aldosterone release was suppressed on the contralateral site (A/C-adrenal vein/A/C-VCI ratio = 0.8). CONCLUSION: AVS is a useful tool for localizing unilateral autonomous adenoma. However, selective sampling often fails on the right adrenal vein, which limits its significance. In this case the A/C-adrenal vein/A/C-VCI in combination with the posture test should be utilized. CT or MRI are of limited value.

Alpha(2A)-adrenoceptors regulate sympathetic transmitter release in mice kidneys.

BACKGROUND AND PURPOSE: In the present study, a rodent model was used to investigate whether the alpha(2A)-adrenoceptor (alpha(2A)) represents the presynaptic autoinhibitory receptor regulating sympathetic transmitter release in the kidney. Moreover, the potential role of alpha(2A) as a heteroceptor regulating adenosine triphosphate (ATP) release was tested. EXPERIMENTAL APPROACH: Kidneys from wild-type (WT) and alpha(2A)-knockout (KO) mice were isolated and perfused. Renal nerves were stimulated with platinum-electrodes. Endogenously released noradrenaline (NA) was measured by HPLC. The perfusion pressure was monitored continuously. KEY RESULTS: Renal nerve stimulation (RNS) induced a frequency (1,2,5,7.5,10,15 Hz)-dependent release of NA in WT mice (994+/-373, 2355+/-541, 6375+/-950, 11626+/-1818, 19138+/-2001 pg NA g(-1) kidney (means+/-s.e.m.)). There was a 2.7-fold (5 Hz) increase of NA release in alpha(2A)-KO mice. In WT animals alpha-adrenoceptor blockade by phentolamine increased RNS-induced NA release in a concentration-dependent manner up to 350% of control. No facilitation by phentolamine was observed in alpha(2A)-KO mice. Pressor responses to 1 Hz and 2 Hz were resistant to alpha(1)-adrenoceptor blockade (0.03 microM prazosin) but abolished by P(2) receptor blockade (5 microM PPADS). Blockade of alpha(2)-adrenoceptors (1 microM rauwolscine) increased these purinergic pressor responses to 296+/-112% (1 Hz) in WT but not in alpha(2A)-KO mice. Exogenous ATP (100 microM) increased basal but not RNS-induced NA release. CONCLUSIONS AND IMPLICATIONS: alpha(2A)-Adrenoceptor-activation inhibits NA and ATP release from renal sympathetic nerves. Pressor responses to RNS at higher stimulation frequencies (>2 Hz) are mediated by NA. At lower frequencies neuronally released ATP seems to be the predominant transmitter mediating renovascular resistance.

Dihydrotachysterol therapy for hypoparathyroidism: consequences of inadequate monitoring. Five cases and a review.

BACKGROUND: The half synthetic Vitamin D analogue dihydrotachysterol (DHT) is widely used for hypocalcaemic hypoparathyroidism following surgical removal of parathyroids. Such treatment generally initiated by surgeons right after surgery has to be continued in clinical practice. Unfortunately, the required careful monitoring of calcium metabolism is often lacking and as demonstrated may lead to life-threatening conditions. PATIENTS AND METHODS: Here we report on five patients referred to our nephrology unit because of unknown impairment of renal function during therapy with DHT. All patients had clinical signs of hypercalcaemia. Since most symptoms are nonspecific they were not perceived by primary care physicians. In fact DHT treatment was continued for 4 - 50 years. In all cases calcium levels were determined after inadequate long intervals ranging from 3.08 to 4.97 mmol/l. Creatinine levels ranged from 277 to 365 micromol/l. All patients suffered from symptoms of severe hypercalcaemia, three of them needing intensive care unit treatment. RESULTS: All patients were treated effectively with a regimen consisting of intravenous saline, a loop diuretic, and application of bisphosphonates. As confirmed by renal biopsy persisting alleviation of renal function was due to calcifications. After discontinuation of DHT therapy patients were safely switched to shorter acting vitamin D derivates maintaining a normal calcium level. CONCLUSIONS: In comparison to short acting vitamin-D derivates hypercalcaemic episodes with DHT appear to last longer and may therefore occur with higher incidence. A future option could be the use of synthetic parathyroid hormone (s-PTH) recently shown to be safe and effective. Nevertheless a customized therapy and careful monitoring is indispensable in any case to prevent irreversible organ damage.