Clinical presentation and genetic variants in patients with autoinflammatory diseases: results from the German GARROD registry.

To investigate clinical symptoms and genetic variants in patients from the German anti-IL-1 registry for autoinflammatory orphan diseases (GARROD) between 2013 and 2022. Multicentre, retrospective analysis of demographic, clinical and genetic data of patients with autoinflammatory diseases (AID) who received anti-IL-1 targeted therapy. The cohort comprised 152 patients with familial Mediterranean fever (FMF; n = 71), cryopyrin-associated periodic syndromes (CAPS; n = 43), TNF-receptor associated periodic syndrome (TRAPS; n = 19), mevalonate kinase deficiency (MKD; n = 3) and unclassified AID (uAID; n = 16). Inflammatory attacks started in 61.2% of the patients before the age of 18 years. The delay between the first AID attack and anti-IL-1 therapy was 17.8 years. Monogenetic AIDs were diagnosed by clinical symptoms. Genetic analyses confirmed the diagnosis in 87.3% of patients with FMF, 65.2% with CAPS and 94.8% with TRAPS. Among this group, heterozygous MEFV variants and variants of unknown significance (VUS) were detected in 22.5% of patients with FMF, 51.2% with CAPS and 47.4% with TRAPS. Patients with VUS were older at disease onset which is consistent with a milder phenotype. Twenty-four patients had secondary AA amyloidosis (AA) at initiation of anti-IL-1 therapy. The mean age of these patients was 16.4 years at their first attack and 44.9 years at the time of AA diagnosis. Turkish-Armenian ancestry correlated with MEFV variants and higher FMF disease activity compared to German ancestry. Molecular genetic analyses should substantiate the clinical diagnosis of a monogenetic AID. Our data support the concept of variable penetrance of VUS which can be associated with late-onset AID.

Results from a national survey on COVID-19-associated mucormycosis in Germany: 13 patients from six tertiary hospitals.

BACKGROUND: Most COVID-19-associated mucormycosis (CAM) cases are reported from India and neighbouring countries. Anecdotally cases from Europe have been presented. OBJECTIVE: To estimate the disease burden and describe the clinical presentation of CAM in Germany. METHODS: We identified cases through German mycology networks and scientific societies, and collected anonymised clinical information via FungiScope®. RESULTS: We identified 13 CAM cases from six tertiary referral hospitals diagnosed between March 2020 and June 2021. Twelve patients had severe or critical COVID-19, eleven were mechanically ventilated for a median of 8 days (range 1-27 days) before diagnosis of CAM. Eleven patients received systemic corticosteroids. Additional underlying medical conditions were reported for all but one patient, five were immunocompromised because of malignancy or organ transplantation, three were diabetic. Eleven patients developed pneumonia. Mortality was 53.8% with a median time from diagnosis of mucormycosis to death of 9 days (range 0-214 days) despite treatment with liposomal amphotericin B and/or isavuconazole in 10 of 13 cases. CAM prevalence amongst hospitalised COVID-19 patients overall (0.67% and 0.58% in two centres) and those admitted to the intensive care unit (ICU) (1.47%, 1.78% and 0.15% in three centres) was significantly higher compared to non-COVID-19 patients (P < .001 for respective comparisons). CONCLUSION: COVID-19-associated mucormycosis is rare in Germany, mostly reported in patients with comorbidities and impaired immune system and severe COVID-19 treated in the ICU with high mortality compared to mainly rhino-orbito-cerebral CAM in patients with mild COVID-19 in India. Risk for CAM is higher in hospitalised COVID-19 patients than in other patients.

Exploring the Impact of Short- and Long-Term Hydrocortisone Replacement on Cognitive Function, Quality of Life and Catecholamine Secretion: A Pilot Study.

Hydrocortisone (HC) substitution is essential in the treatment for patients with adrenal insufficiency (AI). Current replacement regimens however only incompletely mimic the physiological circadian rhythm of cortisol secretion, thereby resulting in subclinical temporary hypo- and hypercortisolism. Several studies point toward impairment of cognitive functions under these conditions, in part due to affected catecholamine secretion. Aim of this study was to evaluate the influence of long-term versus short-term HC replacement therapy on the adrenomedullary system and cognitive functions. Fourteen patients with primary or secondary AI were divided into two groups, depending on the duration of disease and HC replacement therapy (<15 years). All subjects underwent standardized neurocognitive testing; in addition, cortisol and catecholamine levels as well as physiological parameters and quality of life (QoL) were assessed. Patients with HC replacement therapy ≥15 years (n = 7) received significantly higher equivalent glucocorticoid doses than those with a shorter lasting therapy (n = 7; p = 0.048). Neuropsychological tests, QoL, physiological parameters, and cortisol levels did not differ significantly between both groups. Of note, norepinephrine levels were significantly lower in patients on short-term HC replacement therapy (p = 0.025). However, there were no significant differences in catecholamines with respect to the underlying pathophysiology, gender, or age. Irrespective of the duration of use, male patients scored significantly better for single aspects of QoL, whereas females performed significantly better in the attention test. Overall, we showed that duration of cortisol replacement therapy may have an impact on catecholamine release, but does not seem to affect cognitive functions and QoL.

Evidence that CXCL16 is a potent mediator of angiogenesis and is involved in endothelial progenitor cell chemotaxis : studies in mice with K/BxN serum-induced arthritis.

OBJECTIVE: To examine the possibility that CXCL16 recruits endothelial cells (ECs) to developing neovasculature in rheumatoid arthritis (RA) synovium. METHODS: We utilized the RA synovial tissue SCID mouse chimera system to examine human microvascular EC (HMVEC) and human endothelial progenitor cell (EPC) recruitment into engrafted human synovium that was injected intragraft with CXCL16-immunodepleted RA synovial fluid (SF). CXCR6-deficient and wild-type (WT) C57BL/6 mice were primed to develop K/BxN serum-induced arthritis and evaluated for angiogenesis. HMVECs and EPCs from human cord blood were also examined for CXCR6 expression, by immunofluorescence and assessment of CXCL16 signaling activity. RESULTS: CXCR6 was prominently expressed on human EPCs and HMVECs, and its expression on HMVECs could be up-regulated by interleukin-1ß. SCID mice injected with CXCL16-depleted RA SF exhibited a significant reduction in EPC recruitment. In experiments using the K/BxN serum-induced inflammatory arthritis model, CXCR6(-/-) mice showed profound reductions in hemoglobin levels, which correlated with reductions in monocyte and T cell recruitment to arthritic joint tissue compared to that observed in WT mice. Additionally, HMVECs and EPCs responded to CXCL16 stimulation, but exhibited unique signal transduction pathways and homing properties. CONCLUSION: These results indicate that CXCL16 and its receptor CXCR6 may be a central ligand/receptor pair that is closely associated with EPC recruitment and blood vessel formation in the RA joint.

Renal tubular acidosis type IV in hyperkalaemic patients--a fairy tale or reality?

OBJECTIVE: Hyperkalaemia is a common feature in hospitalized patients and often attributed to drugs antagonizing the renin-angiotensin-aldosterone system (RAAS) and/or acute kidney injury (AKI), despite significantly preserved glomerular filtration rate (GFR). The objective of this study was to determine the prevalence and role of renal tubular acidosis type IV (RTA IV) in the development of significant hyperkalaemia. DESIGN: A single-centre retrospective study. PATIENTS: Patients admitted to a University Hospital over 12 months. MEASUREMENTS: Patients with a potassium value > 6·0 mm were identified. Clinical and laboratory data were revisited, and patients with a normal anion gap metabolic acidosis were evaluated for the existence of RTA IV. RESULTS: A total of 57 patients having significant hyperkalaemia (>6·0 mm) were identified. Twelve patients had end-stage renal disease, while 21 patients had solely AKI or progressive chronic renal failure. RTA IV was present in 24 patients (42%), of whom 71% had pre-existing renal insufficiency because of diabetic nephropathy or tubulointerstitial nephritis. All hyperkalaemic patients with urinary/serum electrolytes suggestive of RTA IV had evidence of AKI, but creatinine levels were significantly lower (P < 0·05), while the number of drugs antagonizing the RAAS was comparable. CONCLUSION: We demonstrated that RTA IV (i) is very common in patients with hyperkalaemia; (ii) should always be suspected in hyperkalaemic patients with only moderately impaired GFR; and (iii) may result in significant hyperkalaemia in the presence of both AKI and drugs antagonizing the RAAS.

High prevalence of fibromyalgia-associated symptoms in patients with hypothalamic-pituitary disorders.

OBJECTIVES: Various complaints of patients with fibromyalgia often resemble clinical features observed in patients with hypothalamic-pituitary diseases. The aim of this study was to evaluate whether patients with hypothalamic-pituitary diseases are at increased risk for fibromyalgia syndrome (FMS). METHODS: A questionnaire for evaluating fibromyalgia-associated symptoms was sent to 121 patients with hypothalamic-pituitary disorders (HPD) (60 women, 61 men; mean age, 55.4 years; range, 21-83 years) of the endocrine outpatient clinic. 115 patients (57 women, 58 men; mean age 56.9 years; range, 21 to 82 years) with cardiovascular diseases (CD) served as controls. RESULTS: Fibromyalgia-associated symptoms regarding muscular complaints were significantly more frequent in the HPD group than in CD patients (53.7 % vs. 35.7%, p= 0.003). In particular, we found a significant higher prevalence of autonomic symptoms in the HPD group as compared to the CD group regarding several qualities (cold hands, p=0.039; flatulence, p=0.022; tiredness, p=0.017). In addition, swollen and painful finger joints were reported more often in the HPD group than in the CD group (p=0.002). Of note, no differences regarding any fibromyalgia-associated symptom were detected when patients with hypothalamic-pituitary hormone excess syndromes were compared to those with a pituitary pathology without hormonal excess. Similarly, prevalence of fibromyalgia-associated symptoms was not related to the treatment modality of pituitary disease; i.e. surgical vs. conservative or any hormonal replacement therapy. CONCLUSIONS: Our data suggest that patients with hypothalamic-pituitary disorders may be at increased risk of developing fibromyalgia-associated symptoms.

Evaluation of simple diagnostic parameters in acute kidney injury in hospitalized patients-diagnostic recommendations for non-nephrologists.

Acute kidney injury (AKI) is very common in hospitalized patients, affecting patient's mortality and morbidity. Major causes are prerenal AKI and acute tubular necrosis (ATN). Even though a variety of parameters/indices exist, their reliability and practicability are controversial: in fact, there is a need for a simple diagnostic approach for AKI in in-patients with parameters easily obtained in any hospital. The objective of the study was: (1) to assess reliability of simple laboratory parameters/indices to differentiate pre-/intrarenal AKI; (2) to evaluate the most reliable and feasible parameters/indices; and (3) to identify the possible impact of confounding factors. Retrospectively, in-patients with AKI hospitalized in 2020 in a university nephrology department were included. Spot urine and 24-h collection urine was analyzed with urine sodium (UNa), urine specific gravity (USG), fractional excretion of sodium (FENa), fractional excretion of urea (FEUrea), urine osmolality (UOsm), urine to plasma creatinine ratio (UCr/PCr) and renal failure index (RFI). Overall, 431 patients were included. UNa, UOsm, USG and RFI showed high specificity > 85% for prerenal AKI, UNa and RFI provided good specificity for ATN. Loop diuretics, ACE inhibitors/AT1 blockers or pre-existing chronic kidney disease had no impact. In patients with AKI, UNa, USG and RFI: (1) proved to be very specific for prerenal AKI and showed high sensitivity for ATN; (2) can be easily determined using serum and spot urine; and (3) are not confounded by medication or comorbidities. These parameters/indices are helpful to identify the aetiology of AKI and to guide therapy, thereby improving patients' safety and outcome.

Pre-existing chronic kidney disease, aetiology of acute kidney injury and infection do not affect renal outcome and mortality.

BACKGROUND: We aimed to study the role of aetiology, pre-existing chronic kidney disease (CKD) and infections in acute kidney injury (AKI) on renal outcome and mortality. METHODS: This retrospective study analysed patients with AKI admitted to a university nephrology department from January 1st, 2020 through December 31st, 2020. Aetiology of AKI, underlying renal disease in case of pre-existing CKD and presence of infections were assessed. Development of renal function and risk of death were studied with follow-up until January 31st, 2023. RESULTS: Of 1402 patients screened, 432 patients (30.8%, 67.9 ± 15.4 years) fulfilled the inclusion criteria, half of the population presented with advanced CKD. Even though CKD patients were more often in need of chronic dialysis at time of discharge (6.9% vs 4.5%, p < .001), duration of hospital stay was shorter and in-hospital mortality tended to be lower when compared to AKI without prior renal disease. Neither aetiology of AKI nor pre-existing CKD had an impact on the combined endpoint of end-stage kidney disease and mortality (log rank 0.433 and 0.909). Overall, septic patients showed the highest in-hospital mortality (23.5%) and longest hospital stay (30.0 ± 22.8 days, p < .001), while patients with urosepsis had the shortest hospitalisation time (9.7 days) with lowest risk for dialysis (4.4%). Of note, outcome did not differ in patients with AKI when considering the infectious status. CONCLUSIONS: Overall renal outcome and mortality in AKI patients were not affected by the cause of AKI, pre-existent CKD or infectious status. Only severity of AKI had a negative impact on outcome.

Tunneled central venous catheters for hemodialysis-unfairly condemned? Catheter-related complications in a university hospital setting.

BACKGROUND: Central venous catheters (CVCs) provide an immediate hemodialysis access but are considered to be of elevated risk for complications. It remains unclear, if CVCs per se have relevant impact on clinical outcome. We provide an assessment of CVC-associated complications and their impact on mortality. METHODS: In a single center retrospective study, CVC patients between JAN2015-JUN2021 were included. Data on duration of CVC use, complications and comorbidities was collected. Estimated 6-month mortality was compared to actual death rate. RESULTS: About 478 CVCs were analyzed. Initiation of dialysis was the main reason for CVC implantation. Death was predominant for termination of CVC use. Infections were rare (0.6/1000 catheter days), complications were associated with certain comorbidities. Actual 6-month mortality was lower than predicted (14.3% vs 19.6%). CONCLUSION: (1) CVCs are predominantly implanted for initiation of hemodialysis; (2) serious complications are rare; (3) complications are associated with certain comorbidities; and (4) CVC patients survive longer than predicted.

Beneficial effects of integrin αvß3-blocking RGD peptides in early but not late phase of experimental glomerulonephritis.

BACKGROUND: Integrin αvß3 plays an important role in the regulation of cell proliferation and neoangiogenesis. We found mesangial de novo expression of integrin αvß3 in mesangioproliferative glomerulonephritis (MesGN). The aim of the study was to clarify if blockade of αvß3 integrin with the specific αvß3-blocking cyclic peptide RGDdFV (cRGD) has beneficial effects on the course of this disease. METHODS: Habu snake venom (Habu) GN was induced in male C57BL/6 mice 1 week after uninephrectomy (6 mg Habu toxin/kg body weight intravenously). After 24 h, nephritic animals received αvß3-inhibitory cRGD or cRAD control peptides for 3 or 7 days, respectively. The kidneys were investigated using morphometry, immunohistochemistry and TaqMan polymerase chain reaction. RESULTS: At Day 3, serum creatinine and albuminuria were lower after cRGD compared to cRAD treatment. At Day 3, glomerulosclerosis index, percentage of glomerular injury, mesangial cell (MC) number and volume density of mesangial matrix were significantly lower (P < 0.05) in cRGD-treated mice than in cRAD-treated controls. At Day 7, only a mild effect of cRGD on mesangial matrix expansion and fibronectin messenger RNA was still detectable (P < 0.05). Complementary in vitro studies in MCs revealed that inhibition of αvß3 by cRGD-blocked adhesion, reduced proliferation and increased apoptosis of MCs. CONCLUSION: Habu GN inhibition of integrin αvß3 by cRGD partly ameliorates early injury but has no or only mild effects on late glomerular lesions.

Computed tomography angiography in patients with suspected pulmonary embolism-too often considered?

BACKGROUND: Pulmonary embolism (PE) is a major cause of morbidity and mortality associated with surgery and medical illnesses. In recent years, pulmonary computed tomography angiography (CTA) has become the diagnostic method of choice. However, it remains unclear when to perform CTA and how often a decision based on clinical judgment results in positive or negative findings. METHODS: In a retrospective study, 261 patients admitted for suspected PE were evaluated with pulmonary CTA. Decisions to order CTA were based on clinical judgment and optionally quantitative d-dimer assays. Clinical, radiologic, and laboratory data were revisited and compared in patients with and without proven PE. RESULTS: The patients' mean age was 63 ± 1 years; almost 30% of all participants had at least a moderately reduced renal function. Pulmonary CTA demonstrated PE in only 14.9%; both age and sex distribution was comparable in the PE and non-PE group. Proximal deep vein thrombosis or pathologic chest x-rays were significantly more likely in patients with PE (P < .001 and P < .05), whereas echocardiography results were comparable. d-dimer values were noticeably higher in the PE group (P < .001); however, C-reactive protein and troponin T levels were not helpful. CONCLUSIONS: Pulmonary CTA confirmed PE in only a minority of patients and may be overused. Clinical judgment in conjunction with d-dimer evaluation was of limited help to predict positive results but surprisingly comparable with previous results using pretest probability scoring systems. Using present and previous data, a simplified enhanced algorithm is proposed to reduce use of CTA.

Erythrocyte Sedimentation Rate in Patients with Renal Insufficiency and Renal Replacement Therapy.

BACKGROUND: Determination of the erythrocyte sedimentation rate (ESR) is a simple diagnostic tool for estimating systemic inflammation. It remains unclear whether ESR is influenced by renal disease or renal replacement therapy (RRT). OBJECTIVE: To report the incidence and extent of ESR elevations in patients with chronic kidney disease (CKD) and the possible impact of RRT. METHODS: We performed a single-center, retrospective study in inpatients with or without renal disease and in those with RRT, comparing ESR levels and other laboratory and clinical information. RESULTS: A total of 203 patients were included. On average, ESR was elevated (mean [SD], 51.7 [34.6] mm/h), with no statistically significant difference between the patient groups. Only those receiving PD showed significantly higher ESR (78.3 [33.1] mm/h; P < .001). CONCLUSIONS: ESR testing can be used without restriction in patients with CKD and in patients undergoing hemodialysis and who have received kidney transplantation; however, this measurement should be monitored carefully in patients with PD.

Asymptomatic sustained ventricular fibrillation in a patient with left ventricular assist device.

Optimal medical treatment, cardiac resynchronization, and the use of an implantable cardioverter defibrillator are established therapies of severe congestive heart failure. In refractory cases, left ventricular assist devices are more and more used not only as bridging to cardiac transplantation but also as destination therapy. Ventricular arrhythmias may represent a life-threatening condition and often result in clinical deterioration in patients with congestive heart failure. We report a case of asymptomatic sustained ventricular fibrillation with preserved hemodynamics caused by a nonpulsatile left ventricular assist device. Consecutive adequate but unsuccessful discharges of the implantable cardioverter defibrillator were the only sign of the usually fatal arrhythmia, prompting the patient to consult emergency services. Electrolyte supplementation and initiation of therapy with amiodarone followed by external defibrillation resulted in successful restoration of a stable cardiac rhythm after 3.5 hours.

Interleukin 18 induces angiogenesis in vitro and in vivo via Src and Jnk kinases.

BACKGROUND: Interleukin 18 (IL-18) is a novel mediator of angiogenesis in rheumatoid arthritis (RA). OBJECTIVE: To examine the role of IL-18 in RA angiogenesis and the signalling mechanisms involved. METHODS: Human dermal microvascular endothelial cell (HMVEC) chemotaxis, capillary morphogenesis assays and Matrigel plug angiogenesis assays were performed in vivo using IL-18 with or without signalling inhibitors. A novel model of angiogenesis was devised using dye-tagged HMVECs to study their homing into RA and normal (NL) synovial tissues (STs) engrafted in severe combined immunodeficient (SCID) mice. RESULTS: IL-18-mediated angiogenesis depended on Src and Jnk, as the inhibitors of Src and Jnk blocked IL-18-induced HMVEC chemotaxis, tube formation and angiogenesis in Matrigel plugs. However, inhibitors of Janus kinase 2, p38, MEK, phosphatidylinositol-3-kinase and neutralising antibodies to vascular endothelial growth factor or stromal derived factor-1α did not alter IL-18-induced HMVEC migration. These results were confirmed with Jnk or Src sense or antisense oligodeoxynucleotides. Moreover, IL-18 induced phosphorylation of Src and Jnk in HMVECs. As proof of principle, IL-18 null mice had a significantly decreased angiogenesis compared with wild-type mice in Matrigel plug angiogenesis assays in vivo. IL-18 markedly enhanced mature HMVEC homing to human RA ST compared with NL ST in SCID mice, confirming the role of IL-18-induced angiogenesis in RA ST in vivo. CONCLUSION: Targeting IL-18 or its signalling intermediates may prove to be a potentially novel therapeutic strategy for angiogenesis-dependent diseases, such as RA.

Characterization and outcome following Puumala virus infection: a retrospective analysis of 75 cases.

BACKGROUND: Infection with the Puumala virus (PUUV), which belongs to the Hantavirus family, is a common but often neglected cause of acute kidney injury (AKI) in endemic areas of Europe. The objective of the present study was to systematically analyse clinical presentation and renal outcomes following PUUV infection. METHODS: In a retrospective study, we analysed data from 75 patients who were admitted to two large hospitals in Germany over an 8-year period and who tested positive for PUUV infection. Clinical and laboratory data were collected from patient files; creatinine levels before admission and during follow-up were obtained from phone calls. RESULTS: Patients were between 16 and 82 years old (average +/- SD, 40.4 +/- 13.4) with a male to female ratio of 2.5:1. They showed a wide variety of clinical presentations with renal failure being the cause of admission in only 50%. AKI developed in 95% of patients who showed maximum creatinine levels of 4.3 +/- 0.3 mg/dl. Four patients required temporary dialysis, and one patient died from pulmonary complications. Thrombocytopaenia (137 +/- 11 x 10(3)/microl) was present in almost all cases, and elevated levels of lactate dehydrogenase (LDH) and C-reactive protein (CRP) were observed in 57 and 100% of patients, respectively. Urinalysis revealed mild to nephrotic proteinuria in 85%, which was often associated with haemoglobinuria. All patients showed full recovery of renal function and return to pre-existing normal serum creatinine levels. CONCLUSION: In a majority of cases, PUUV infection results in thrombocytopenic AKI. Fever is a requirement for diagnosis, while elevated LDH and CRP values are also frequently observed. Overall, early renal outcomes were excellent.

Malposition of a haemodialysis catheter in a hepatic vein.

An immediate need for haemodialysis therapy often requires placement of a central vein catheter, which is sometimes complicated by catheter malposition. This report presents the case of a 16-year-old male with end-stage renal disease and a non-functioning central haemodialysis catheter. A chest X-ray identified a very uncommon position of the catheter's tip in a hepatic vein. Management consisted of catheter replacement, resulting in an excellent outcome without sequelae.

Relative incidence of thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome in clinically suspected cases of thrombotic microangiopathy.

BACKGROUND: Data are lacking on the relative incidence of thrombotic thrombocytopenic purpura (TTP), haemolytic uraemic syndrome (HUS) caused by Shiga toxin-producing Escherichia coli (STEC) and atypical HUS (aHUS) in patients presenting with thrombotic microangiopathies (TMAs). METHODS: This was a prospective, cross-sectional, multicentre and non-interventional epidemiological study. Patients fulfilling criteria for TMAs (platelet consumption, microangiopathic haemolytic anaemia and organ dysfunction) were included in the study. The primary objective was to assess the relative incidence of TTP, STEC-HUS, aHUS and 'other' physician-defined diagnoses. The secondary objective was to develop an algorithm to predict a severe deficiency in ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) activity (≤10%) using routine laboratory parameters. A post hoc classification using the recent Kidney Disease: Improving Global Outcomes diagnostic criteria was then undertaken to further classify patient groups. RESULTS: aHUS was diagnosed with a relative incidence of 61%, whereas TTP, STEC-HUS and 'other' were diagnosed in 13, 6 and 20% of patients, respectively. In the post hoc analysis, 27% of patients with a TMA were classified as 'primary aHUS' and 53% as 'secondary aHUS'. Multivariate analysis revealed that severe deficiency in ADAMTS13 activity (≤10%) was unlikely to underlie TMA if platelet and serum creatinine were above threshold values of 30 × 109/L and 1.8 mg/dL, respectively (negative predictive value of 92.3 and 98.1, respectively, if one or both values were above the threshold). CONCLUSIONS: In this study, aHUS was the most common single diagnosis among patients presenting with a TMA. In the absence of an ADAMTS13 activity result, platelet count and serum creatinine may aid in the differential diagnosis.

Practical approaches to the management of autosomal dominant polycystic kidney disease patients in the era of tolvaptan.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease worldwide. The renal phenotype is characterized by progressive cystic enlargement of the kidneys leading to a decline in renal function, hypertension and often end-stage renal disease (ESRD). Supportive care with blood pressure control and management of pain, urinary infections and renal stone disease has, until recently, been the mainstay of treatment. With the recent approval of tolvaptan for use in ADPKD, the disease progression may now be targeted specifically. Algorithms that guide treatment initiation have been proposed but a more pragmatic and patient-individualized approach is often needed to make decisions regarding therapy. It is highly important to identify ADPKD patients with rapidly progressive disease who are likely to benefit most from this treatment and avoid treatment in patients that are unlikely to reach ESRD. METHODS AND RESULTS: Here we present a series of cases of ADPKD patients in whom therapy with tolvaptan has been considered and report the rationale for the treatment decisions based on available lifestyle, clinical, biochemical, radiological and genetic data. CONCLUSIONS: These cases provide a discussion for the use of tolvaptan in ADPKD within the nephrology clinic and allow insights into the practicalities of using this therapy outside of clinical trials.