Mieneke Rook

Nephrectomy Elicits Impact of Age and BMI on Renal Hemodynamics: Lower Postdonation Reserve Capacity in Older or Overweight Kidney Donors

Renal functional reserve could be relevant for the maintenance of renal function after kidney donation. Low‐dose dopamine induces renal vasodilation with a rise in glomerular filtration rate (GFR) in healthy subjects and is thought to be a reflection of reserve capacity (RC). Older age and higher body mass index (BMI) may be associated with reduced RC. We therefore investigated RC in 178 consecutive living kidney donors (39% males, age 48 ± 11 years, BMI 25.5 ± 4.1). RC was determined as the rise in GFR (125I‐iothalamate), 4 months before and 2 months after donor nephrectomy. Before donor nephrectomy, GFR was 114 ± 20 mL/min, with a reduction to 72 ± 12 mL/min after donor nephrectomy. The dopamine‐induced rise in GFR of 11 ± 10% was reduced to 5 ± 7% after donor nephrectomy (p < 0.001). Before donor nephrectomy, older age and higher BMI did not affect reserve capacity. After donor nephrectomy, the response of GFR to dopamine independently and negatively correlated with older age and higher BMI. Moreover, postdonation reserve capacity was absent in obese donors. The presence of overweight had more impact on loss of RC in younger donors. In conclusion, donor nephrectomy unmasked an age‐ and overweight‐induced loss of reserve capacity. Younger donors with obesity should be carefully monitored.

Association of Urinary Biomarkers With Disease Severity in Patients With Autosomal Dominant Polycystic Kidney Disease: A Cross-sectional Analysis

BACKGROUND Disease monitoring of autosomal dominant polycystic kidney disease (ADPKD) will become more important with potential upcoming therapeutic interventions. Because serum creatinine level is considered of limited use and measurement of effective renal blood flow (ERBF) and total renal volume are time consuming and expensive, there is a need for other biomarkers. We aimed to investigate which urinary markers have increased levels in patients with ADPKD; whether these urinary markers are associated with measured glomerular filtration rate (mGFR), ERBF, and total renal volume; and whether these associations are independent of albuminuria (urine albumin excretion [UAE]). STUDY DESIGN Diagnostic test study. SETTING & PARTICIPANTS 102 patients with ADPKD (Ravine criteria) and 102 age- and sex-matched healthy controls. INDEX TEST 24-hour urinary excretion of glomerular (immunoglobulin G), proximal tubular (kidney injury molecule 1 [KIM-1], N-acetyl-β-d-glucosaminidase, neutrophil gelatinase-associated lipocalin [NGAL], and β(2)-microglobulin), and distal tubular (heart-type fatty acid binding protein [H-FABP]) damage markers and inflammatory markers (monocyte chemotactic protein 1 [MCP-1] and macrophage migration inhibitory factor). REFERENCE TEST Disease severity assessed using measures of kidney function (mGFR and ERBF, measured using clearance of iothalamate labeled with iodine 125 and hippuran labeled with iodine 131 during continuous infusion, respectively) and structure (total renal volume, measured using magnetic resonance imaging). OTHER MEASUREMENTS 24-hour UAE. RESULTS In 102 patients with ADPKD (aged 40 ± 11 years; 58% men), levels of all measured urinary biomarkers were increased compared with healthy controls. Excretion of immunoglobulin G and albumin relatively were most increased. ERBF and mGFR values were associated with urinary excretion of β(2)-microglobulin, NGAL, and H-FABP independent of UAE, whereas total renal volume was associated with KIM-1, NGAL, and MCP-1 independent of UAE. LIMITATIONS Cross-sectional, single center. CONCLUSIONS Levels of markers for multiple parts of the nephron are increased in patients with ADPKD. In addition to measurement of UAE, measurement of urinary β(2)-microglobulin, KIM-1, H-FABP, MCP-1, and especially NGAL could be of value for determination of disease severity in patients with ADPKD.

Predictive capacity of pre-donation GFR and renal reserve capacity for donor renal function after living kidney donation

Kidney transplantation from living donors is important to reduce organ shortage. Reliable pre‐operative estimation of post‐donation renal function is essential. We evaluated the predictive potential of pre‐donation glomerular filtration rate (GFR) (iothalamate) and renal reserve capacity for post‐donation GFR in kidney donors.

Renal Function Equations before and after Living Kidney Donation: A Within-Individual Comparison of Performance at Different Levels of Renal Function

BACKGROUND AND OBJECTIVES The Modification of Diet in Renal Disease (MDRD) study equation and the Cockcroft-Gault (CG) equation perform poorly in the (near-) normal range of GFR. Whether this is due to the level of GFR as such or to differences in individual characteristics between healthy individuals and patient with chronic kidney disease (CKD) is unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We evaluated the performance of MDRD, CG per BSA (CG/(BSA)) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations compared with measured GFR (mGFR; I-iothalamate) at 4 months before and 2 months after donation in 253 consecutive living kidney donors. RESULTS mGFR declined from 103 ± 15 to 66 ± 11 ml/min per 1.73 m(2) after donation. All equations underestimated mGFR at both time points. Arithmetic performance analysis showed improved performance after donation of all equations, with significant reduction of bias after donation. Expressed as percentage difference, mGFR-estimated GFR (eGFR) bias was reduced after donation only for CG/(BSA). Finally, in 295 unselected individuals who were screened for donation, mGFR was below the cutoff for donation of 80 ml/min per 1.73 m(2) in 19 individual but in 166, 98, and 74 for MDRD, CDK-EPI, and CG/(BSA), respectively. CONCLUSIONS A higher level of GFR as such is associated with larger absolute underestimation of true GFR by eGFR. For donor screening purposes, eGFR should be interpreted with great caution; when in doubt, true GFR should be performed to prevent unjustified decline of prospective kidney donors.

Early Renal Abnormalities in Autosomal Dominant Polycystic Kidney Disease

BACKGROUND AND OBJECTIVES Potential therapeutic interventions are being developed for autosomal dominant polycystic kidney disease (ADPKD). A pivotal question will be when to initiate such treatment, and monitoring disease progression will thus become more important. Therefore, the prevalence of renal abnormalities in ADPKD at different ages was evaluated. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Included were 103 prevalent ADPKD patients (Ravine criteria). Measured were mean arterial pressure (MAP), total renal volume (TRV), GFR, effective renal plasma flow (ERPF), renal vascular resistance (RVR), and filtration fraction (FF). Twenty-four-hour urine was collected. ADPKD patients were compared with age- and gender-matched healthy controls. RESULTS Patients and controls were subdivided into quartiles of age (median ages 28, 37, 42, and 52 years). Patients in the first quartile of age had almost the same GFR when compared with controls, but already a markedly decreased ERPF and an increased FF (GFR 117 +/- 32 versus 129 +/- 17 ml/min, ERPF 374 +/- 119 versus 527 +/- 83 ml/min, FF 32% +/- 4% versus 25% +/- 2%, and RVR 12 (10 to 16) versus 8 (7 to 8) dynes/cm(2), respectively). Young adult ADPKD patients also had higher 24-hour urinary volumes, lower 24-hour urinary osmolarity, and higher urinary albumin excretion (UAE) than healthy controls, although TRV in these young adult patients was modestly enlarged (median 1.0 L). CONCLUSIONS Already at young adult age, ADPKD patients have marked renal abnormalities, including a decreased ERPF and increased FF and UAE, despite modestly enlarged TRV and near-normal GFR. ERPF, FF, and UAE may thus be better markers for disease severity than GFR.

Effects of preexistent hypertension on blood pressure and residual renal function after donor nephrectomy.

Background. Living kidney donor selection has become more liberal with acceptation of hypertensive donors. Here, we evaluate short-term and 1- and 5-year renal outcome of living kidney donors with preexistent hypertension. Methods. We compared outcome of hypertensive donors by gender, age, and body mass index with matched control donors. Hypertension was defined as predonation antihypertensive drug use. All donors had glomerular filtration rate (125I-iothalamate) and effective renal plasma flow (131I-hippuran) measured 4 months before and 2 months after donation. A subset of donors had serum creatinine measured 1 year after donation or a renal function measurement 5 years after donation. Results. Included were 47 hypertensive donors and 94 control donors (both 53% male; mean age, 57±7 years; and body mass index, 28±4 kg/m2). Pre- and early postdonation, systolic blood pressure, and mean arterial pressure were significantly higher in hypertensive donors. Control donors showed a rise in diastolic blood pressure after donation, and thus the predonation difference was lost postdonation. Both at 1 year (29 hypertensive donors, 58 controls) and 5 years after donation (13 hypertensive donors and 26 controls) blood pressure was similar. Renal function was similar at all time points. Discussion. In summary, hypertensive living kidney donors have similar outcome in terms of blood pressure and renal function as control donors, early and 1 and 5 years after donation.

Donor kidney adapts to body dimensions of recipient: no influence of donor gender on renal function after transplantation.

Female kidneys and kidneys from small donors have been suggested to perform worse after kidney transplantation. Here, we evaluate the impact of gender and body dimensions on posttransplantation GFR in living donor transplantation. Two hundred and ninety‐three donor–recipient pairs, who were transplanted at our center were evaluated. All pairs had detailed renal function measurement (125I‐iothalamate and 131I‐hippuran) 4 months predonation in the donor and 2.5 months posttransplantation in donor and recipient. For 88 pairs, 5 years of recipient follow‐up was available. Delta GFR was calculated as (recipient GFR–donor single kidney GFR). Recipients of both male and female kidneys had similar renal function at early and long term after transplantation. Male recipients had higher ERPF, ΔGFR and ΔERPF at both time points. Kidneys of donors smaller than their recipient had higher ΔGFR and ΔERPF than kidneys of larger donors at both time points (p < 0.05). In multivariate analysis, ΔGFR was predicted by donor/recipient BSA‐ratio together with transplantation related factors (R2 0.19), irrespective of donor and recipient gender. In conclusion, in living donor transplantation, female kidneys perform as well as male donor kidneys. Kidneys adapt to the recipients body size and demands, independent of gender, without detrimental effects in renal function and outcome up to mid‐long term.

Influence of lung nodule margin on volume- and diameter-based reader variability in CT lung cancer screening

OBJECTIVE: To evaluate the influence of nodule margin on inter- and intrareader variability in manual diameter measurements and semi-automatic volume measurements of solid nodules detected in low-dose CT lung cancer screening. METHODS: 25 nodules of each morphological category (smooth, lobulated, spiculated and irregular) were randomly selected from 93 participants of the Dutch-Belgian Randomized Lung Cancer Screening Trial (NELSON). Semi-automatic volume measurements were performed using Syngo LungCARE® software (Version Somaris/5 VB10A-W, Siemens, Forchheim, Germany). Three radiologists independently measured mean diameters manually. Impact of nodule margin on interreader variability was evaluated based on systematic error and 95% limits of agreement. Interreader variability was compared with the nodule growth cut-off as used in Lung CT Screening Reporting and Data System (LungRADS; +1.5-mm diameter) and the Dutch-Belgian Randomized Lung Cancer Screening Trial(acronym: NELSON) /British Thoracic Society (+25% volume). RESULTS: For manual diameter measurements, a significant systematic error (up to 1.2 mm) between readers was found in all morphological categories. For semi-automatic volume measurements, no statistically significant systematic error was found. The interreader variability in mean diameter measurements exceeded the 1.5-mm cut-off for nodule growth for all morphological categories [smooth: ±1.9 mm (+27%), lobulated: ±2.0 mm (+33%), spiculated: ±3.5 mm (+133%), irregular: ±4.5 mm (+200%)]. The 25% vol growth cut-off was exceeded slightly for spiculated [28% (+12%)] and irregular [27% (+8%)] nodules. CONCLUSION: Lung nodule sizing based on manual diameter measurement is affected by nodule margin. Interreader variability increases especially for nodules with spiculated and irregular margins, and causes substantial misclassification of nodule growth. This effect is almost neglectable for semi-automated volume measurements. Semi-automatic volume measurements are superior for both size and growth determination of pulmonary nodules. ADVANCES IN KNOWLEDGE: Nodule assessment based on manual diameter measurements is susceptible to nodule margin. This effect is almost neglectable for semi-automated volume measurements. The larger interreader variability for manual diameter measurement results in inaccurate lung nodule growth detection and size classification.

Renal hemodynamics in overweight and obesity: pathogenetic factors and targets for intervention

Weight excess is a risk factor for progressive renal function loss, not only in subjects with renal disease or renal transplant recipients, but also in the general population. Considering the increasing prevalence of obesity worldwide, weight excess may become the main renal risk factor on a population basis, all the more so because the risk is not limited to morbid obesity, but is already apparent in the overweight range. The mechanism of the renal risk is multifactorial. In addition to the role of comorbid conditions such as hypertension and diabetes, current evidence supports a pathogenetic role for renal hemodynamics, specifically glomerular hyperfiltration, and also glomerular hypertension. Weight excess is associated with an elevated glomerular filtration rate and a less pronounced rise in renal plasma flow, resulting in an elevated filtration fraction. This suggests glomerular hypertension due to afferent–efferent dysbalance, which impairs glomerular protection from systemic hypertension. Data in renal transplant recipients support the pathogenetic role of elevated glomerular pressure for long-term renal prognosis. Blockade of the renin–angiotensin–aldosterone system can reverse the renal hemodynamic abnormalities. The obesity-associated renal risk is unfavourably affected by high sodium intake. This may be due to the effects of sodium on blood pressure, which is often sodium-sensitive in obesity, but direct renal effects are also present. Interestingly, sodium restriction ameliorates overweight-associated hyperfiltration in overweight subjects. More focus on weight excess as a renal risk factor is warranted. Preventive measures should focus on weight excess as well as on specific protection against renal damage, by renin–angiotensin–aldosterone system-blockade and moderate sodium restriction.

Donor Kidney Adapts to Body Dimensions of Recipient

Female kidneys and kidneys from small donors have been suggested to perform worse after kidney transplantation. Here, we evaluate the impact of gender and body dimensions on posttransplantation GFR in living donor transplantation. Two hundred and ninety‐three donor–recipient pairs, who were transplanted at our center were evaluated. All pairs had detailed renal function measurement (125I‐iothalamate and 131I‐hippuran) 4 months predonation in the donor and 2.5 months posttransplantation in donor and recipient. For 88 pairs, 5 years of recipient follow‐up was available. Delta GFR was calculated as (recipient GFR–donor single kidney GFR). Recipients of both male and female kidneys had similar renal function at early and long term after transplantation. Male recipients had higher ERPF, ΔGFR and ΔERPF at both time points. Kidneys of donors smaller than their recipient had higher ΔGFR and ΔERPF than kidneys of larger donors at both time points (p < 0.05). In multivariate analysis, ΔGFR was predicted by donor/recipient BSA‐ratio together with transplantation related factors (R2 0.19), irrespective of donor and recipient gender. In conclusion, in living donor transplantation, female kidneys perform as well as male donor kidneys. Kidneys adapt to the recipients body size and demands, independent of gender, without detrimental effects in renal function and outcome up to mid‐long term.