Severe hypotension requiring resuscitation in tumour-related carotid sinus syndrome: a case report.

Background: An uncommon cause of reflex syncope is carotid sinus syndrome (CSS). In rare cases, this can be caused by compression of the carotid sinus by a progressive or invasive tumour. Case summary: A 57-year-old female was presented at the emergency department with recurrent syncope in the morning. After initial observation, no heart rhythm abnormalities or syncope were observed. The day after discharge, she was presented again with a syncope. Hypotension and bradycardia were observed this time. Furthermore, a mass in the neck area was found near the carotid artery. She was admitted to the cardiology department with suspected carotid sinus syndrome for telemetric observation. Diagnostics by biopsy and PET-CT showed a metastasized squamous cell carcinoma of the tongue. Initial treatment of dexamethasone was started after which the recurrence of the syncope decreased. However, during admission, an in-hospital cardiac arrest occurred due to persistent vagal stimulation. As a result, the patient was started on neoadjuvant chemotherapy and midodrine, after which she experienced multiple complications and died. Discussion: To the best of our knowledge, this is the first case report that shows an IHCA due to severe hypotension related to a carotid sinus syndrome.

Tubular secretion of creatinine in autosomal dominant polycystic kidney disease: consequences for cross-sectional and longitudinal performance of kidney function estimating equations.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by renal tubular cell proliferation and dedifferentiation, which may influence tubular secretion of creatinine (CCr[TS]). STUDY DESIGN: Diagnostic test study. SETTING & PARTICIPANTS: We therefore investigated CCr(TS) in patients with ADPKD and controls and studied consequences for the performance of glomerular filtration rate (GFR) estimating equations. INDEX & REFERENCE TESTS: In patients with ADPKD and healthy controls, we measured GFR as (125)I-iothalamate clearance while simultaneously determining creatinine clearance. OTHER MEASUREMENTS: 24-hour urinary albumin excretion. RESULTS: In 121 patients with ADPKD (56% men; mean age, 40 ± 11 [SD] years) and 215 controls (48% men; mean age, 53 ± 10 years), measured GFR (mGFR) was 78 ± 30 and 98 ± 17 mL/min/1.73 m(2), respectively, and CCr(TS) was 15.9 ± 10.8 and 10.9 ± 10.6 mL/min/1.73 m(2), respectively (P < 0.001). The higher CCr(TS) in patients with ADPKD remained significant after adjustment for covariates and appeared to be dependent on mGFR. Correlation and accuracy between mGFR and CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) estimated GFR (eGFR) were 0.95 and 99%, respectively; between mGFR and MDRD (Modification of Diet in Renal Disease) Study eGFR, they were 0.93 and 97%, respectively. Values for bias, precision, and accuracy were similar or slightly better than in controls. In addition, change in mGFR during 3 years of follow-up in 45 patients with ADPKD correlated well with change in eGFR. LIMITATIONS: Cross-sectional, single center. CONCLUSIONS: CCr(TS) in patients with ADPKD is higher than that in controls, but this effect is limited and observed at only high-normal mGFR. Consequently, the CKD-EPI and MDRD Study equations perform relatively well in estimating GFR and change in GFR in patients with ADPKD.

SLC22A2 is associated with tubular creatinine secretion and bias of estimated GFR in renal transplantation.

Genome-wide association studies reported SLC22A2 variants to be associated with serum creatinine. As SLC22A2 encodes the organic cation transporter 2 (OCT2), the association might be due to an effect on tubular creatinine handling. To test this hypothesis we studied the association of SLC22A2 polymorphisms with phenotypes of net tubular creatinine secretion: fractional creatinine excretion (FEcreat) and bias of estimated glomerular filtration rate (eGFR). We also studied the association with end-stage renal disease (ESRD) and graft failure (GF) in renal transplant recipients. SLC22A2 single nucleotide polymorphisms (SNPs), rs3127573 and rs316009, were genotyped in 1,142 ESRD patients receiving renal transplantation and 1,186 kidney donors as controls. GFR was measured with (125)I-iothalamate clearance. Creatinine clearance was also assessed. FEcreat was calculated from the simultaneous clearances of creatinine and (125)I-iothalamate. Donor rs316009 was associated with FEcreat (beta -0.053, P = 0.024) and with estimated [modification of diet in renal disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)] but not measured GFR. In line with this, donor rs316009 was associated with bias of the MDRD and CKD-EPI but not the Cockroft-Gault equation. Both SNPs were associated with ESRD: odds ratios [95% CI] 1.39 [1.16-1.67], P = 0.00065, and 1.23 [1.02-1.48], P = 0.042, for rs3127573 and rs316009, respectively. Neither SNP was associated with GF. Thus, SLC22A2 is associated with phenotypes of net tubular creatinine secretion and ESRD.

Creatinine excretion rate and mortality in type 2 diabetes and nephropathy.

OBJECTIVE: The creatinine excretion rate (CER) is inversely associated with mortality in the general and renal transplant population. The CER is a marker for muscle mass. It is unknown whether the CER is associated with outcome in diabetes. We therefore investigated whether the CER is a determinant of all-cause mortality in diabetic patients. RESEARCH DESIGN AND METHODS: We used data from the combined Reduction of Endpoints in Non-insulin dependent diabetes mellitus with the Angiotensin II Antagonist Losartan (RENAAL) and Irbesartan Diabetic Nephropathy Trial (IDNT) studies. A total of 1,872 patients (58% of the overall population) with type 2 diabetes and nephropathy with valid 24-h urinary creatinine excretion data were included. The primary end point of the analyses was all-cause mortality. RESULTS: Mean age was 60 ± 8 years and median CER was 1,407 (total range 400-3,406) mg/day. Body surface area, hemoglobin, black race, and albuminuria were positive independent determinants of the CER, whereas female sex and age were inverse independent determinants of the CER. During a median follow-up of 36 (29-45) months, 300 patients died. In a Kaplan-Meier analysis of sex-stratified tertiles of the CER, risk for all-cause mortality increased with decreasing CER (P < 0.001). In a multivariable Cox regression analysis, lower CER (as a continuous variable) was independently associated with increased risk for all-cause mortality (hazard ratio 0.39 [95% CI 0.29-0.52], P < 0.001). Adjustment for potential collection errors did not materially change these associations. CONCLUSIONS: Lower CER was strongly associated with increased all-cause mortality in patients with type 2 diabetes and nephropathy. As the CER can be considered a proxy for muscle mass, this puts renewed emphasis on physical condition and exercise in this population.

A re-appraisal of volume status and renal function impairment in chronic heart failure: combined effects of pre-renal failure and venous congestion on renal function.

The association between cardiac failure and renal function impairment has gained wide recognition over the last decade. Both structural damage in the form of systemic atherosclerosis and (patho) physiological hemodynamic changes may explain this association. As regards hemodynamic factors, renal impairment in chronic heart failure is traditionally assumed to be mainly due to a decrease in cardiac output and a subsequent decrease in renal perfusion. This will lead to a decrease in glomerular filtration rate and a compensatory increase in tubular sodium retention. The latter is a physiological renal response aimed at retaining fluids in order to increase cardiac filling pressure and thus renal perfusion. In heart failure, however, larger increases in cardiac filling pressure are needed to restore renal perfusion and thus more volume retention. In this concept, in chronic heart failure, an equilibrium exists where a certain degree of congestion is the price to be paid to maintain adequate renal perfusion and function. Recently, this hypothesis was challenged by new studies, wherein it was found that the association between right-sided cardiac filling pressures and renal function is bimodal, with worse renal function at the highest filling pressures, reflecting a severely congested state. Renal hemodynamic studies suggest that congestion negatively affects renal function in particular in patients in whom renal perfusion is also compromised. Thus, an interplay between cardiac forward failure and backward failure is involved in the renal function impairment in the congestive state, presumably along with other factors. Only few data are available on the impact of intervention in volume status on the cardio-renal interaction. Sparse data in cardiac patients as well as evidence from cohorts with primary renal disease suggest that specific targeting of volume overload may be beneficial for long-term outcome, in spite of a certain further decrease in renal function, at least in the context of current treatment where possible reflex neurohumoral activation is ameliorated by the background treatment by blockers of the renin-angiotensin-aldosterone system.

Higher body mass index is associated with higher fractional creatinine excretion in healthy subjects.

BACKGROUND: Accurate glomerular filtration rate (GFR) measurement in normal to high range is important for epidemiological studies and workup for kidney donation. Creatinine-based equations perform poorly in this GFR range. Creatinine clearance (CrCl) provides a substitute, provided urine is collected accurately and tubular creatinine handling can be accounted for. The latter is poorly characterized in the normal GFR range. METHODS: Therefore, we studied performance of CrCl, fractional creatinine excretion (FE(creat)) and its determinants in 226 potential kidney donors (47% males, mean 53 ± 10 years). GFR was assessed as (125)I-iothalamate clearance, simultaneously with 2-h CrCl and 24-h CrCl. RESULTS: Mean GFR was 101 ± 18, 2-h CrCl 110 ± 20 and 24-h CrCl 106 ± 29 mL/min/1.73 m(2). Mean bias of 24 h CrCl was 7.4 [inter-quartile range -6.7 to 20.0] mL/min/1.73 m(2), precision (R(2)) 0.39 and 30% accuracy 82%. Mean FE(creat) was 110 ± 11%. FE(creat) correlated with body mass index (BMI) (r = 0.34, P < 0.001). Consequently, bias of 24-h CrCl increased from 2.7 (inter-quartile range -6.5 to 16.7) to 8.6 (inter-quartile range -5.8 to 20.5) and 12.6 (inter-quartile range 7.0 to 25.4) mL/min in subjects with BMI <25, 25-30 and >30 kg/m(2), respectively (P < 0.05). On multivariate analysis, BMI and gender were predictors of FE(creat). CONCLUSIONS: CrCl systematically overestimates GFR in healthy subjects. The overestimation significantly correlates with BMI, with higher FE(creat) in subjects with higher BMI. The impact of BMI on tubular creatinine secretion can be accounted for, when using CrCl for GFR assessment in the normal to high range, by the following formula: GFR = 24-h CrCl - (22.75 + 0.76 × BMI - 0.29 × mean arterial pressure (-6.11 if female).

Erythropoietin is reduced by combination of diuretic therapy and RAAS blockade in proteinuric renal patients with preserved renal function.

BACKGROUND: Renin-angiotensin-aldosterone system (RAAS) blockade improves prognosis in renal patients, but usually requires diuretic co-treatment. RAAS blockade can decrease erythropoietin (EPO) and/or haemoglobin (Hb) levels. Diuretics decrease EPO in rodents, but their effect on EPO and Hb in humans is unknown. METHODS: Proteinuric renal patients with preserved renal function were treated during 6-week periods with placebo, losartan 100 mg/day (LOS) and LOS plus hydrochlorothiazide 25 mg/day (LOS/HCT), in random order. RESULTS: Hb was inversely related to proteinuria, and EPO levels were inappropriately low in relation to Hb. Hb was lowered by LOS with and without HCT. EPO was decreased by LOS/HCT, but not by LOS. CONCLUSIONS: EPO and Hb are reduced by HCT added to LOS in proteinuric renal patients with preserved renal function. We hypothesize that EPO reduction by HCT is caused by a decrease in renal oxygen requirement, which is the main stimulus for EPO production, due to the inhibition of active tubular sodium reabsorption. Further studies should explore the exact mechanism of this phenomenon and its clinical impact.