His bundle pacing insights from electroanatomical mapping: Topography and pacing targets.

OBJECTIVES: To characterize 3D electroanatomical mapping (EAM) of the His bundle (HB) region. BACKGROUND: Visualization of selective (S) and nonselective (NS) HB capture areas by EAM has not been described and may help guide HB pacing (HBP). METHODS: EAM was performed via NavX system in 17 patients (pts) undergoing HBP. HB cloud, S-HB, NS-HB, and right bundle (RB) capture areas were mapped. RESULTS: S-HBP areas were identified in 11, NS-HBP in 14, and RB in 11 pts. Two NS-HBP areas (upper and lower) either separated by S-HBP (8 pts) or almost contiguous (5 pts) were observed. S-HBP area measured: 1.1 ± 0.9 cm2 , NS upper: -1.2 ± 0.9 cm2 , NS lower: -1.2 ± 0.9 cm2 , RB: -1.7 ± 1.3 cm2 , total His cloud: -4.1 ± 2.7 cm2 . Electrocardiogram (ECG) pacemaps were different between upper and lower NS-HBP areas in 13/14 pts (p = .006). ECG differences between NS clouds were present in inferior leads in 9 pts (more negative QRS complex from lower NS area) and in precordial leads in 5 pts. There was no correlation between HBP lead location and capture threshold. R-wave amplitude was higher at more distal locations on HB cloud (p = .02). CONCLUSION: (1) Pacemapping identifies distinct regions that may correspond to HB anatomy. (2) A linear S-HBP area is typically surrounded by two separate NS areas. (3) Pace-map ECGs from upper and lower NS-HBP areas have different morphologies. (4) These EAM features and pace-mapping may be helpful to the implanter.

Hospital-acquired acute kidney injury and hospital readmission: a cohort study.

BACKGROUND: Hospital-acquired acute kidney injury (AKI) is associated with increased mortality and resource consumption. Little is known about the association of AKI with short-term hospital readmissions. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: We investigated whether adult survivors of hospital-acquired AKI were at increased odds for early hospital readmission. PREDICTOR: The peak-to-nadir serum creatinine difference during the index hospitalization was used to define AKI according to the KDIGO (Kidney Disease: Improving Global Outcomes) classification and staging system. MEASUREMENTS: Multivariable logistic regression analyses examined the association of AKI with 30-, 60-, and 90-day hospital readmission, adjusting for age, sex, race, Charlson-Deyo comorbidity index score, acute hospital-related factors, common causes of hospitalization, and baseline estimated glomerular filtration rate. RESULTS: 3,345 (15%) of 22,001 included patients experienced AKI during the index hospitalization. Compared to the non-AKI group, the AKI group had a significantly higher 30-day hospital readmission rate (11% vs 15%; P<0.001), which persisted at 60 and 90 days. The AKI group also was more likely to be readmitted to the hospital within 30 days for cardiovascular-related conditions, mainly heart failure (P<0.001) and acute myocardial infarction (P=0.01). AKI associated independently with higher odds of 30-day hospital readmission (OR, 1.21; 95% CI, 1.08-1.36), which persisted at 60 (OR, 1.15; 95% CI, 1.03-1.27) and 90 days (adjusted OR, 1.13; 95% CI, 1.02-1.25). Results were attenuated in a propensity score-matched cohort of 5,912 patients. LIMITATIONS: Single-center study of mild forms of AKI; ascertainment bias and outcome misclassification due to the use of administrative codes. CONCLUSIONS: Our results suggest that survivors of hospital-acquired AKI experience higher odds of early hospital readmission. Transitions of care services may be warranted for such patients to prevent readmissions and reduce health care costs.

The Characteristics and Outcomes of Nonhospitalized Patients With Heart Failure in Saudi Arabia: A Contemporary Single-Center Study.

Background Contemporary data on patients with heart failure (HF) in Saudi Arabia is limited. Methods This was a retrospective study of patients who were followed in the HF Clinic at our center after January 1, 2022. The study end date was August 31, 2023. Patients who were alive and followed for <6 months were excluded. We reported the clinical characteristics, utilization of established therapies for HF, proportion of potential candidates for ancillary HF treatments, and rates of HF events and mortality. Results A total of 202 patients met the study criteria. The mean age was 56.0 ± 15.2 years. The median follow-up from the initial visit to the study end date was 47 months (interquartile range {IQR}: 29-58 months). Coronary artery disease (CAD) was the cause of HF in 85 (42%) patients. At their latest visit, 103 (51%) patients had diabetes, 82 (41%) were obese, and 134 (66%) received quadruple therapy. Iron deficiency was present in 143 (71%) patients during follow-up. At their latest visit, moderate-to-severe or severe functional mitral regurgitation (MR) and hyperkalemia were present in 15 (7%) and 20 (10%) patients, respectively. The combined annual rate of HF hospitalization and emergency visits for HF was 20%. At least one hospitalization for HF within a year before the study end date occurred in 19 (9%) patients. The annual all-cause mortality was 1.8%. Conclusion This contemporary cohort of outpatients with HF was relatively young and had a high prevalence of diabetes, obesity, and iron deficiency. An estimate of potential candidates for iron replacement, transcatheter repair of the mitral valve, novel potassium binders, and the implantation of the pulmonary artery pressure monitor was among the first reported regionally. All-cause mortality was low, yet the burden of HF-related events was significant.

Dose of erythropoiesis-stimulating agents and adverse outcomes in CKD: a metaregression analysis.

BACKGROUND: Targeting higher hemoglobin levels with erythropoiesis-stimulating agents (ESAs) to treat the anemia of chronic kidney disease (CKD) is associated with increased cardiovascular risk. STUDY DESIGN: Metaregression analysis examining the association of ESA dose with adverse outcomes independent of target or achieved hemoglobin level. SETTING & POPULATION: Patients with anemia of CKD irrespective of dialysis status. SELECTION CRITERIA FOR STUDIES: We searched MEDLINE (inception to August 2010) and bibliographies of published meta-analyses and selected randomized controlled trials assessing the efficacy of ESAs for the treatment of anemia in adults with CKD, with a minimum 3-month duration. Two authors independently screened citations and extracted relevant data. Individual study arms were treated as cohorts and constituted the unit of analysis. PREDICTORS: ESA dose standardized to a weekly epoetin alfa equivalent, and hemoglobin levels. OUTCOMES: All-cause and cardiovascular mortality, cardiovascular events, kidney disease progression, or transfusion requirement. RESULTS: 31 trials (12,956 patients) met the criteria. All-cause mortality was associated with higher (per epoetin alfa-equivalent 10,000-U/wk increment) first-3-month mean ESA dose (incidence rate ratio [IRR], 1.42; 95% CI, 1.10-1.83) and higher total-study-period mean ESA dose (IRR, 1.09; 95% CI, 1.02-1.18). First-3-month ESA dose remained significant after adjusting for first-3-month mean hemoglobin level (IRR, 1.48; 95% CI, 1.02-2.14), as did total-study-period mean ESA dose adjusting for target hemoglobin level (IRR, 1.41; 95% CI, 1.08-1.82). Parameter estimates between ESA dose and cardiovascular mortality were similar in magnitude and direction, but not statistically significant. Higher total-study-period mean ESA dose also was associated with increased rate of hypertension, stroke, and thrombotic events, including dialysis vascular access-related thrombotic events. LIMITATIONS: Use of study-level aggregated data; use of epoetin alfa-equivalent doses; lack of adjustment for confounders. CONCLUSIONS: In patients with CKD, higher ESA dose might be associated with all-cause mortality and cardiovascular complications independent of hemoglobin level.

Out-of-hospital use of proton pump inhibitors and hypomagnesemia at hospital admission: a nested case-control study.

BACKGROUND: Case series suggest that long-term use of proton pump inhibitors (PPIs) is associated with hypomagnesemia, but the current literature lacks systematically collected data. Our aim was to examine whether hypomagnesemia at the time of hospital admission is associated with out-of-hospital use of PPIs. STUDY DESIGN: Nested case-control study matched for age and sex. SETTING & PARTICIPANTS: Data were collected retrospectively from a tertiary acute-care facility. Eligible cases consisted of 402 adults with hypomagnesemia (serum magnesium <1.4 mEq/L) at the time of hospital admission to medical services, age- and sex-matched with 402 control individuals with normal serum magnesium levels (1.4-2.0 mEq/L). PREDICTOR: Out-of-hospital PPI use was identified in the hospital record. An omeprazole equivalent dose was calculated when possible. Covariates included the Charlson-Deyo comorbidity index, diabetes, diuretic use, estimated glomerular filtration rate, and gastroesophageal reflux. OUTCOME: Multivariable conditional logistic regression analyses were used to examine the association of PPI use with hypomagnesemia at the time of hospital admission. RESULTS: PPI use was not associated with hypomagnesemia (adjusted OR, 0.82; 95% CI, 0.61-1.11). Neither PPI type nor omeprazole equivalent daily dose was associated with hypomagnesemia. Sensitivity analyses of PPI use restricted to patients with esophageal disorders (adjusted OR, 1.00; 95% CI, 0.69-1.45), severe hypomagnesemia (magnesium, ≤1.0 mEq/L; adjusted OR, 0.78; 95% CI, 0.13-4.61), or estimated glomerular filtration rate ≥60 mL/min/1.73 m(2) (adjusted OR, 0.84; 95% CI, 0.53-1.34) were unrevealing. LIMITATIONS: Exposure misclassification; hospitalized patients on medical services may not be representative of a broader ambulatory-based population. CONCLUSIONS: In a hospital-based adult population, out-of-hospital PPI use is not associated with hypomagnesemia at the time of hospital admission to medical services. In light of these inconclusive results, prospective cohort studies are needed to address this rare potential medication-related adverse effect.

The Integral Role of Chloride & With-No-Lysine Kinases in Cell Volume Regulation & Hypertension.

Chloride anions are the most abundant in humans. For many years, it has been believed that chloride is simply a counterion of all other cations, ensuring the electroneutrality of the extracellular space. Recent data suggests that chloride anions possess a broad spectrum of important activities that regulate vital cellular functions. It is now evident that, apart from its contribution to the electroneutrality of the extracellular space, it acts as an osmole and contributes to extracellular and intracellular volume regulation. Its anionic charge also contributes to the generation of cell membrane potential. The most interesting action of chloride anions is their ability to regulate the activity of with-no-lysine kinases, which in turn regulate the activity of sodium chloride and potassium chloride cotransporters and govern the reabsorption of salt and excretion of potassium by nephron epithelia. Chloride anions seem to play a crucial role in cell functions, such as cell volume regulation, sodium reabsorption in the distal nephron, potassium balance, and sodium sensitivity, which lead to hypertension. All of these functions are accomplished on a molecular level via complicated metabolic pathways, many of which remain poorly defined. We attempted to elucidate some of these pathways in light of recent advances in our knowledge, obtained mainly from experimental studies.

Left bundle area pacing: Guiding implant depth by ring measurements.

BACKGROUND: Criteria for successful left bundle area pacing (LBAP) are in flux and currently guided by lead tip measurements. Lead ring measurements during LBAP have not been well studied. OBJECTIVE: The purpose of this study was to investigate dynamics in pacing parameters during successful and unsuccessful lead implant attempts. METHODS: SelectSecure 3830 pacing leads (Medtronic, Inc) guided by C315 sheaths for LBAP were placed for standard pacing indications in 73 patients. Retrospective review of procedural, echocardiographic, and standard pacing data were performed. Depth and lead-septal angle of implanted electrodes were determined from fluoroscopy with septal contrast delineation. Depth was graded in 4 categories according to the degree of ring penetration into the septum. Successful implant was defined by the ability to advance the lead deep into the septum and achieve LBAP criteria (ventricular activation time, QRS width/shape). RESULTS: Ring impedance increased stepwise during successful attempts as opposed to unsuccessful attempts (P = .039). A wider lead-septal angle at implant position correlated with higher ring impedance (P = .036), whereas no association was found with tip impedance. Unipolar ring threshold correlated with depth of lead implant (P = .029). Tip impedance measurements at implant position were less predictive of lead depth and did not correlate with septal thickness. CONCLUSION: Ring pacing parameters are more predictive of lead progress than tip measurements. Lead depth and lead-septal angle can be determined from ring impedance measurements. These measurements may provide determination of lead depth and could obviate the need for contrast injection.

Effect of frequent or extended hemodialysis on cardiovascular parameters: a meta-analysis.

BACKGROUND: Increased left ventricular (LV) mass is a risk factor for cardiovascular mortality in patients with chronic kidney failure. More frequent or extended hemodialysis (HD) has been hypothesized to have a beneficial effect on LV mass. STUDY DESIGN: Meta-analysis. SETTING & POPULATION: MEDLINE literature search (inception to April 2011), Cochrane Central Register of Controlled Trials and ClinicalTrials.gov using the search terms "short daily HD," "daily HD," "quotidian HD," "frequent HD," "intensive HD," "nocturnal HD," and "home HD." SELECTION CRITERIA FOR STUDIES: Single-arm cohort studies (with pre- and post-study evaluations) and trials examining the effect of frequent or extended HD on cardiac morphology and function and blood pressure parameters. Studies of hemofiltration, hemodiafiltration, and peritoneal dialysis were excluded. INTERVENTION: Frequent (2-8 hours, >3 times weekly) or extended (>4 hours, 3 times weekly) HD compared with conventional (≤4 hours, 3 times weekly) HD. OUTCOMES: Absolute changes in cardiac morphology and function, including LV mass index (LVMI; primary) and blood pressure parameters (secondary). RESULTS: We identified 38 single-arm studies, 5 crossover trials, and 3 randomized controlled trials. By meta-analysis of 23 study arms, frequent or extended HD significantly reduced LVMI from baseline (-31.2 g/m(2), 95% CI, -39.8 to -22.5; P < 0.001). The 3 randomized trials found a less pronounced net reduction in LVMI (-7.0 g/m(2); 95% CI, -10.2 to -3.7; P < 0.001). LV ejection fraction improved by 6.7% (95% CI, 1.6% to 11.9%; P = 0.01). Other cardiac morphologic parameters showed similar improvements. There also were significant decreases in systolic, diastolic, and mean blood pressure and mean number of antihypertensive medications. LIMITATIONS: Paucity of randomized controlled trials. CONCLUSIONS: Conversion from conventional to frequent or extended HD is associated with improvements in cardiac morphology and function, including LVMI and LV ejection fraction, respectively, and several blood pressure parameters, which collectively might confer long-term cardiovascular benefit. Trials with long-term clinical outcomes are needed.

Metabolic syndrome risk factors and estimated glomerular filtration rate among children and adolescents.

The aim of this study was to seek the possible relationship between estimated glomerular filtration rate (e-GFR) and anthropometric indexes, lipids, insulin sensitivity, and metabolic syndrome risk factors among healthy children and adolescents. Sufficient evidence suggest that obesity is related with a novel form of glomerulopathy named obesity-related glomerulopathy (ORG) among adults, children, and adolescents. Glomerular filtration rate was estimated from serum creatinine in 166 healthy children and adolescents [79 males, 87 females; age 10.6 +/- 3.3 (3-18) years]. Anthropometric indexes and systolic and diastolic blood pressure were measured. Fasting insulin, glucose, creatinine, uric acid, total cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, and triglycerides were estimated. Insulin sensitivity was estimated from known formulas. The presence of certain metabolic syndrome risk factors was checked among the studied population. Boys showed higher e-GFR rates than girls (f = 8.49, p = 0.004). We found a strong positive correlation between e-GFR and body weight (r = 0.415), body mass index (BMI) (r = 0.28), waist circumference (r = 0.419), hip circumference (r = 0.364), birth weight (r = 0.164), systolic blood pressure (SBP) (r = 0.305), and mean arterial pressure (MAP) (r = 0.207). A negative correlation was found between e-GFR and fasting glucose (r = -0.19), total cholesterol (r = -0.27) and LDL-cholesterol (r = -0.26). Clustering of metabolic syndrome risk factors among certain individuals was correlated with higher e-GFR rates (f = 3.606, p = 0.007). The results of this study suggest that gender, anthropometric indexes, and SBP are strong positive determinants of e-GFR among children and adolescents. Waist circumference is the most powerful determinant of e-GFR. Fasting glucose and lipid abnormalities are negative determinants of e-GFR among the studied population. Clustering of metabolic syndrome risk factors is coupled with higher e-GFR rates.

Isolated Renal Artery Dissection: A Systematic Review of Case Reports.

Isolated renal artery dissection (IRAD) is a rare and often unrecognized clinical entity, with a paucity of data on its epidemiology and management. We extracted 129 cases of IRAD from the medical literature between 1972 and 2016. IRAD as a result of an extended dissection from the aorta and splanchnic or mesenteric arteries was excluded. The mean age of presentation was 42.7±12.9 years, with a male predominance (79%). Abdominal pain (75.9%) was the most common presenting symptom. Etiology was more likely to be spontaneous (76%) than traumatic (12%), iatrogenic (9%), or drug-induced (1.5%). The most common risk factors were hypertension (28.7%), fibromuscular dysplasia (8.5%), and Ehlers-Danlos syndrome (5.4%). Unilateral renal artery dissection (right 45.5%, left 40.5%) was more frequent than bilateral (14%). More than half (56.6%) of the cohort were managed medically (blood pressure control and /or anticoagulation). Of those who underwent intervention, endovascular stenting or embolization (35%) was utilized more frequently than nephrectomy or bypass (21%). Computed tomography (CT) and magnetic resonance angiography (MRA) have the highest diagnostic sensitivity (91% and 93%, respectively) as compared to ultrasonography (27%). A high degree of clinical suspicion is required to diagnose IRAD. CT and MRI have a higher diagnostic sensitivity. As compared to invasive management, conservative management has comparable outcomes.

Presence of pseudopolyps in ulcerative colitis is associated with a higher risk for treatment escalation.

BACKGROUND: Pseudopolyps in ulcerative colitis (UC) are considered as indicators of previous episodes of severe inflammation and ulceration of the mucosa. The aim of the study was to investigate the long-term outcomes of patients treated for UC, with or without pseudopolyps. METHODS: This was a retrospective single-center study. Consecutive patients with UC and available endoscopic data from 2000 until 2016 were eligible for the study and were followed until June 2017. Patients with incomplete medical/endoscopic charts or interrupted follow up were excluded from the study. Primary outcomes included time to treatment escalation, treatment escalation to biological agents or surgery, and UC-related hospitalization. RESULTS: Eighty-three UC patients were included in the study, of whom 25 (30%) had pseudopolyps. The median duration of follow up was 2.8 years (interquartile range: 1.1-4.9). Multiple Cox regression analysis identified the presence of pseudopolyps as the only variable independently associated with treatment escalation (hazard ratio [HR] 2.3, 95% confidence interval [CI] 1.2-4.3; P=0.014) and escalation to biological agents or surgery (HR 6.3, 95%CI 1.9-20.7; P=0.002). CONCLUSION: This retrospective single-center study provides the first preliminary evidence that patients with UC and pseudopolyps may represent a subpopulation with a higher inflammatory burden and a greater need for treatment escalation, including to biological agents or surgery. Large, prospective multicenter studies are certainly warranted to confirm these findings.

Permanent His-bundle pacing using stylet-directed, active-fixation leads placed via coronary sinus sheaths compared to conventional lumen-less system.

BACKGROUND: The use of coronary sinus (CS) sheaths to deliver stylet-driven leads (SDLs) for His-bundle pacing (HBP) has not been described. Conventionally, HBP is achieved using a stylet-less lead delivered through a customized catheter. OBJECTIVE: The purpose of this study was to characterize the acute and early-term HBP experience with stylet-driven, active-fixation leads delivered through CS sheaths compared to the conventional approach. METHODS: Delivery of Medtronic 4471 and 7742 SDLs was attempted in 27 patients. Delivery was facilitated using CS guide catheters and custom-shaped stylets. Procedural characteristics and lead performance were compared to those of a group of 17 patients in whom delivery of 3830 lumen-less leads (LLLs) was attempted. Patients had heterogeneous pacing indications. RESULTS: HBP with SDL was successful in 24 of 27 patients(89%) compared to 15 of 17 patients (88%) in the LLL group. Mean procedural and fluoroscopy times in the SDL and LLL groups were 129 ± 43 minutes vs 104 ± 43 minutes and 9.6 ± 5.2 minutes vs 8.3 ± 5.0 minutes, respectively (both P = NS). There was a significant difference in procedure and fluoroscopy times within the SDL group between the first and second halves of the series, probably secondary to a learning curve. Acute HBP thresholds were higher with SDL than with LLL (2.6 ± 1.5 V vs 1.5 ± 1.2 V; P = .02) and remained stable at 8.4 ± 5.3 months. Both SDLs exhibited similar pacing thresholds. Two crossovers between groups occurred (1 in each group). Four patients with SDL and 1 patient with LLL exhibited high thresholds during follow-up. CONCLUSION: Permanent HBP using stylet-driven, active-fixation leads delivered through conventional CS sheaths is feasible. Procedural characteristics and lead performance were clinically acceptable.

Direct Visualization of the His Bundle Pacing Lead Placement by 3-Dimensional Electroanatomic Mapping: Technique, Anatomy, and Practical Considerations.

BACKGROUND: His bundle pacing (HBP) remains technically challenging and is currently guided by electrograms and 2-dimensional fluoroscopy. Our objective was to describe a new technique for HBP directly guided by electroanatomic mapping (EAM). METHODS: Twenty-eight patients were included. The atrioventricular septum was mapped via EAM, and His bundle (HB) electrograms, selective, and nonselective HB capture sites were tagged. Pacing leads were connected to EAM, navigated to tagged HB target sites and deployed. Intracardiac electrograms and pacing parameters were recorded. Lead location was tagged on the cloud of HB sites, which was divided into 3 arbitrary segments. In 5 patients, atrioventricular nodal ablation was performed with direct visualization of the HBP lead by EAM. RESULTS: Reproducible navigation of the pacing lead to predetermined HBP locations guided by EAM was achieved in all patients. The lead was successfully deployed in 25 patients. HB cloud area was 360 (212) mm2. There was no correlation between HBP threshold and lead location on the His cloud. The intracardiac electrograms atrial/ventricular ratio at the lead deployment site correlated with its EAM position on the His cloud ( P=0.045). Procedure, fluoroscopy, and mapping times were 116.0 (38.8), 8.6 (6.3), and 9.0 (11.4) minutes, respectively. HBP threshold at implant was 1.5 (2.3) V at 1.5 (1.0) ms. Distance between HB lead and ablation sites was 10.0 (1.3) mm in patients undergoing atrioventricular nodal ablation. CONCLUSIONS: Direct guidance of HBP by EAM allows for direct visualization of the pacing lead on the HB cloud and reproducible navigation to predetermined HB capture sites. Intracardiac electrograms atrial/ventricular ratio at the lead deployment site correlates with His cloud location. EAM can be applied during standard HBP procedures or combined with atrioventricular nodal ablation.

Molecular pathophysiology of Bartter's and Gitelman's syndromes.

BACKGROUND: In the last two decades, progress in cytogenetic and genome research has enabled investigators to unravel the underlying molecular mechanisms of inherited tubulopathies such as Bartter's and Gitelman's syndromes and helped physicians to better understand not only these two pathologic entities but also renal pathophysiology and salt sensitive hypertension. DATA SOURCES: Articles collected from PubMed and open access journals included original articles, research articles, and comprehensive reviews. They were evaluated by the authors with an special emphasis on originality and up to date information about molecular pathophysiology. RESULTS: Bartter's and Gitelman's syndromes are two different inherited salt loosing tubulopathies. They are characterized by various inability of distal nephron to reabsorb sodium chloride with resultant extarcellular volume contraction and increased activity of the renin angiotensin aldosterone system. Hypokalemic metabolic alkalosis is a common feature of these two forms of tubulopathies. Hypercalciuria characterizes the majority of Bartter's syndrome, and hypomagnesemia with hypocalciuria characterizes Gitelman's syndrome. Low blood pressure is a common feature among patients who suffered from these tubulopathies. Bartter's syndromes encompass a heterogeneous group of ion channels defects localized at the thick ascending limp of Henle's loop with resultant loss of function of sodium-potassium-2 chloride cotransporter. These defects result in the impairment of the countercurrent multiplication system of the kidney as well as calcium, potassium and acid base disturbances which in the majority of cases are proved lethal especially in the antenatal and/or immediate postnatal life period. The underlying pathology in Gitelman's syndrome is defined to the distal convoluted tubule and is related to loss of function of the sodium-chloride cotransporter. The results of this defect encompass the inability of extracellular volume homeostasis, magnesium and potassium conservation, and acid base disturbances which are generally mild and in the majority of cases are not life-threatening. CONCLUSIONS: Recent advances in molecular pathophysiology of Bartter's and Gitelman's syndromes have helped physicians to better understand the underlying mechanisms of these pathologic entities which remain obscure. Data collected from experiments among genetically manipulated animals enable us to better understand the pathophysiology of mammalian kidney and the underlying mechanisms of salt sensitive hypertension and to lay a foundation for the future development of new drugs, especially diuretics and antihypertensive drugs.

The loop of Henle as the milestone of mammalian kindey concentrating ability: a historical review.

The first description of the renal tubules is attributed to Lorenzo Bellini in 1662 and four years later Marcello Malpighi described the glomerulus. In 1842 Sir William Bowman described the capsule that surrounds the Malpighian body and its connection with the renal tubule and introduced the "excretory" hypothesis of urine formation. In the same year, Carl Ludwig introduced the "filtration-reabsorption" hypothesis of urine formation. Bowman's hypothesis was accepted by the so-called "vitalists" and Ludwig's hypothesis by the so-called "mechanists". In the middle of this confliction, Jacob Henle described in 1862 the homonymous "U" shaped loop but his discovery has neglected. In 1942 Werner Kuhn, a physical chemist, proposed that the loop of Henle may be the natural analog of the hairpin countercurrent multiplication system which concentrates urine in mammalian kidneys. In 1951 Kuhn, Hargitay and Wirz showed experimentally that the loop of Henle was the most important part of the countercurrent multiplication system of urine-concentrating mechanism in mammalian kidneys. The new theory was accepted by English-speaking scientists later, in 1958, when Carl Gottschalk and Margaret Mylle published their experimental work and proved that Kuhn's theory was correct. Gottschalk summarized the evidence of the accumulated knowledge in 1962, three centuries after the first description of renal tubules and one century after description of Henle's loop.

A meta-analysis of continuous vs intermittent infusion of loop diuretics in hospitalized patients.

BACKGROUND: Several studies have examined the potential benefits of continuous vs intermittent (bolus) intravenous loop diuretic administration in hospitalized patients with conflicting results. We conducted a meta-analysis to compare the efficacy of these 2 strategies in hospitalized adults and children with extracellular fluid volume expansion. METHODS: We searched MEDLINE (through October 2012) and prior meta-analyses for randomized controlled trials comparing the efficacy of continuous vs intermittent infusion of loop diuretics. Random-effects model meta-analyses were performed to examine several outcomes, including net change in urine output and body weight. RESULTS: We identified 7 crossover and 11 parallel-arm randomized controlled trials (936 patients) of adults and children. In the 15 studies of adults, continuous loop diuretic infusion resulted in a nonsignificant net increase in daily urine output of 334 mL (95% confidence interval [CI], -74 to 742; P = .11) relative to the bolus infusion. In the 8 studies that used a loading dose, continuous loop diuretic infusion resulted in a significant net increase in daily urine output of 294 mL (95% CI, 31-557; P = .03) relative to the intermittent infusion. There was also a significant net decrease in body weight of 0.78 kg (95% CI, -1.54 to -0.03; P = .04) in the continuous relative to the intermittent loop diuretic infusion. In the 3 studies of children, there was no demonstrable effect on daily urine output or body weight. CONCLUSION: Continuous infusion of loop diuretics preceded by a loading dose results in greater diuresis in hospitalized adults with extracellular fluid volume expansion compared with intermittent dosing regimens. Further studies are required to examine whether these benefits translate into improved clinical outcomes.

World incidence of AKI: a meta-analysis.

BACKGROUND AND OBJECTIVES: The burden of AKI around the globe has not been systematically examined. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A systematic review (2004-2012) of large cohort studies was conducted to estimate the world incidence of AKI and its stages of severity and associated mortality, and to describe geographic variations according to countries, regions, and their economies. AKI definitions were reclassified according to the Kidney Disease Improving Global Outcomes (KDIGO) staging system. Random-effects model meta-analyses and meta-regressions were used to generate summary estimates and explore sources of heterogeneity. RESULTS: There were 312 studies identified (n=49,147,878) , primarily in hospital settings. Most studies originated from North America, Northern Europe, and Eastern Asia, from high-income countries, and from nations that spent ≥5% of the gross domestic product on total health expenditure. Among the 154 studies (n=3,585,911) that adopted a KDIGO-equivalent AKI definition, the pooled incidence rates of AKI were 21.6% in adults (95% confidence interval [95% CI], 19.3 to 24.1) and 33.7% in children (95% CI, 26.9 to 41.3). The pooled AKI-associated mortality rates were 23.9% in adults (95% CI, 22.1 to 25.7) and 13.8% in children (95% CI, 8.8 to 21.0). The AKI-associated mortality rate declined over time, and was inversely related to income of countries and percentage of gross domestic product spent on total health expenditure. CONCLUSIONS: Using the KDIGO definition, 1 in 5 adults and 1 in 3 children worldwide experience AKI during a hospital episode of care. This analysis provides a platform to raise awareness of AKI with the public, government officials, and health care professionals.