- Email: [email protected]
Is preeclampsia a risk for end-stage renal disease?
commentary
Is preeclampsia a risk for end-stage renal disease? Claudio Ponticelli1 and Gabriella Moroni2 Little information is available about the risk of end-stage renal disease (ESRD) after preeclampsia. The review of Covella et al. demonstrated that former preeclamptic women have a significant risk of ESRD in the medium term. However, it is still unknown which preeclamptic woman are at higher risk for progressive kidney disease. After delivery, women who had preeclampsia, particularly those with persistent hypertension, symptomatic proteinuria, or microalbuminuria, should receive a regular checkup for kidney disease. Kidney International (2019) 96, 547–549; https://doi.org/10.1016/j.kint.2019.05.009 Copyright ª 2019, International Society of Nephrology. Published by Elsevier Inc. All rights reserved.
see clinical investigation on page 711
T
he placenta is central to the pathogenesis of preeclampsia. During a normal pregnancy, trophoblasts invade the uterus and induce remodeling of the spiral arteries to nourish the fetus, which allows the arteries to settle placental blood flow independent of maternal vasomotor changes. In women with preeclampsia, a defective cytotrophoblast invasion of the uterine spiral arteries occurs. The lumen of these arteries remains narrow and results in poor placental perfusion and hypoxia. Further arrival of blood flow and new oxygen to a hypoxic placenta may create a condition of ischemia-reperfusion that, coupled with maternal susceptibility, leads to the release of reactive oxygen species and anti-angiogenic factors, such as the soluble fms-like protein kinase 1, inflammatory cytokines, and agonistic angiotensin II type-1 receptor autoantibodies. Each of these factors has been shown to induce hypertension experimentally through the production of endothelin-1.1 This potent vasoconstrictor aggravates endothelial lesions by inducing proinflammatory 1 Division of Nephrology Ospedale Maggiore, Milano, Italy (retired); and 2Unita’ Operativa di Nefrologia e Dialisi Fondazione IRCCS Ca’ Granda Ospedale Maggiore di Milano, Italy
Correspondence: Claudio Ponticelli, Ampere 126, 20131 Milano, Italy. E-mail: ponticelli.claudio@ gmail.com Kidney International (2019) 96, 540–554
mechanisms and increases vascular resistance, leading to hypertension. In the glomeruli, the endothelial cells are swollen and demonstrate loss of fenestrations, which allows fibrinoid deposits and accumulation of fluids and lipids, leading to glomerular enlargement and ischemia. This glomerular endotheliosis may result in glomerular dysfunction, podocyturia, and proteinuria.2 Garovic et al.3 first demonstrated that urinary podocyte excretion occurred in patients with preeclampsia. Nephrin and synaptopodin were seen in the urine before proteinuria appeared. The predictive value for the diagnosis of preeclampsia was greater for podocyturia than for any of the measured angiogenic factors. Measures to prevent or attenuate preeclampsia, such as low-dose aspirin, calcium, diet, and lifestyle interventions, showed potential but small benefit. The only measure to cure preeclampsia rests on delivery. However, preterm delivery may result in complications for the newborn, with their incidence and severity being inversely related to the length of pregnancy. In the presence of early preeclampsia (<34 weeks of gestation) or mild hypertension (<160/ 110 mm Hg), treatment may help delay delivery. Preeclampsia management includes oral or intravenous medication to control blood pressure and prevent seizures and steroid injections to speed up the development of the fetal lungs.
However, in cases of intractable hypertension, seizures, thrombocytopenia, coagulopathy, or a syndrome with hemolysis, elevated liver enzymes, and low platelets, delivery should be induced as soon as possible to prevent morbidity and mortality in the mother and fetus. After delivery, blood pressure and proteinuria usually return to pre-pregnancy levels in the mother. For the newborn, prematurity and growth restriction may happen if delivery occurs, respectively, before 37 weeks and 32 weeks. A main problem for the mother is represented by long-term consequences. A concern is the possibility that preeclampsia might lead to permanent kidney damage in women without preexisting chronic kidney disease (CKD). Whether the endothelial lesions that develop during preeclampsia actually reverse after delivery is unknown, because a control kidney biopsy usually is not performed after pregnancy in women with normal renal function. It also is unknown whether soluble fmslike protein kinase 1, inflammatory cytokines, and agonistic angiotensin II type-1 receptor autoantibodies are still altered after delivery.4 On the other hand, microalbuminuria may persist in some women after preeclampsia, which is an indirect sign of persistent vascular and glomerular damage. Thus it would be possible to hypothesize that endothelial dysfunction disrupts the mechanism of vascular homeostasis regulation, predisposing the vessel wall to vasoconstriction, platelet activation, and thrombosis that eventually may result in persisting arterial hypertension and CKD. In addition, a contributory role may be played by podocyturia. The loss of podocytes in urine loss and the reduced expression of nephrin in podocytes recovered from preeclamptic women2,3 may be the index of severe cytoskeleton disorganization, which may result in glomerular and podocyte hypertrophy. If the glomerular growth exceeds the capacity of podocytes to adapt and adequately cover some parts of the filtration surface, podocytes may detach from the glomerular basement membrane. The podocyte loss may lead to glomerular basement membrane denudation and proteinuria, whereas the 547
commentary
Preeclampsia—delivery
Double checkup at 2, 4 and 6 months
Normal blood pressure; neither albuminuria nor podocyturia
Blood pressure ≥ 140/90 mm Hg or proteinuria ≥ 1 g/day
Microalbuminuria and/or podocyturia
No increased risk of CKD and ESRD
Increased risk of CKD and ESRD
Long-term risk of CKD and ESRD
Standard health checkups
Frequent (2–3 months) renal checkups Antihypertensive therapy RAS inhibitors
Renal checkup every year
Figure 1 | Suggested algorithm for women who had preeclampsia. A renal checkup should include at least a clinical visit with a measurement of blood pressure, blood cell count, serum creatinine, estimated glomerular filtration rate, urinalysis with dosage of proteinuria (measured in g/24 h or protein-to-creatinine ratio in spot urine sample), and sediment analysis. If possible, the presence of podocytes should be investigated in cytocentrifuged urine by evaluating the expression of podocalyxin in nucleated or multinucleated cells by immunofluorescence. CKD, chronic kidney disease; ESRD, end-stage renal disease; RAS, renin-angiotensin system.
contact of detached podocytes with Bowman’s capsule can activate parietal epithelial cells that migrate to the glomerular tuft via the denuded glomerular basement membrane. From this entry site, parietal epithelial cells produce extracellular matrix, eventually leading to a focal glomerulosclerosis that may result in proteinuria and CKD. A few years ago, a systematic review of retrospective studies highlighted the association between preeclampsia and persistent postpartum microalbuminuria. This review included 273 women with preeclampsia and 333 women with uncomplicated pregnancies. At a mean of 7.1 years after giving birth, 31% of former preeclamptic women had microalbuminuria compared with 7% of women with uncomplicated pregnancies, a 4-fold increased risk, similar to that of patients with diabetes mellitus type 1. Women with severe preeclampsia had an 8-fold increased risk of microalbuminuria. No difference in serum creatinine or in estimated glomerular filtration rate was seen between women 548
with preeclampsia and control subjects.5 However, criteria of inclusion in the study required a period of at least 6 months after delivery. In many participants, this follow-up period was too short to evaluate the potential risk of CKD and ESRD. After that review, a few long-term studies reported contradictory results. Two large multicenter reports that included patients with follow-up periods of 10 years or more outlined an increased risk of ESRD in women who experienced preeclampsia or hypertensive disorders during pregnancy.6,7 On the other hand, a study that investigated proteinuria and renal function in former preeclamptic women 10 years after giving birth demonstrated only a high-normal estimated glomerular filtration rate and a slightly higher protein excretion.8 To better assess the long-term renal risk of preeclampsia, Covella et al.9 performed a systematic review and a metaanalysis by selecting 21 papers, including 11 meta-analyses, published after 2000. Only papers reporting follow-ups of at least 4 years were selected. The review
reported that the relative risk of ESRD was significantly greater (6.35) in 110,803 women who had preeclampsia in comparison with 2,680,929 control subjects without preeclampsia. The risk of developing albuminuria or CKD increased in preeclamptic women, but the difference with control subjects was not significant. In translating meta-analytic risk into the number of patients with preeclampsia who needed follow-up to detect one adverse event, 310 patients were needed to identify one woman with ESRD. Covella et al.9 should be congratulated for their tremendous efforts in disentangling so many heterogeneous papers. However, they could not elucidate whether the risk of ESRD is related to the presence of underlying diseases that predisposed to the development of preeclampsia or to the severity of preeclampsia or to every form of preeclampsia. Until further data identify patients at high risk for long-term ESRD, we believe that, every 2 months and for at least 6 to 12 months, patients who had preeclampsia should undergo a renal Kidney International (2019) 96, 540–554
commentary
checkup consisting of evaluation of blood pressure, serum creatinine, estimated glomerular filtration rate, microalbuminuria, and urine sediment (including research for podocytes or their components, when possible). CKD is unlikely to develop in women who do not show any renal abnormality after this period. Patients with persistent proteinuria or hypertension after delivery are at risk for ESRD. Those patients should undergo a frequent check of renal parameters and should be treated with antihypertensive drugs, including inhibitors of the renin-angiotensin system in case of proteinuria. The more difficult group is that of asymptomatic women with microalbuminuria. Is this an innocent bystander or an early sign of an endothelial dysfunction that may increase the risk of kidney disease over time? These women should be monitored for long-term periods, but one checkup per year is probably sufficient (Figure 1). Other points remain uncertain. The review included retrospective studies performed in different countries. The criteria for selecting participants and the management of preeclamptic women were probably different. These variables can have influenced the results. The review has the merit of considering patients who had a follow-up of at least 4 years after preeclampsia. Such a period, although longer than those of previous studies, is too short to assess the true risk of ESRD. Finally, it is strange that the risk of ESRD was significantly associated with preeclampsia whereas the risk of CKD was not significantly associated with preeclampsia. One might suspect that many patients with CKD were not diagnosed and treated in due time. However, in spite of these limitations, the message that preeclampsia may represent a risk factor for ESRD is clear and has clinical relevance. In summary, women who experienced preeclampsia are at increased risk of the development of ESRD in the long term. However, retrospective studies, although accurate, cannot identify which patients are at risk of progressive kidney disease. Long-term, prospective studies would be necessary. While waiting for Kidney International (2019) 96, 540–554
solid indications, long-term monitoring of renal parameters is recommended for former preeclamptic women, in particular for those who have persistent hypertension, proteinuria, or even isolated microalbuminuria after delivery. DISCLOSURE All the authors declared no competing interests. REFERENCES 1. George EM, Granger JP. Endothelin key mediator in preeclampsia. Am J Hypertens. 2011;24:964–969. 2. Craici IM, Wagner SJ, Weissgerber TL, et al. Advances in pathophysiology of preeclampsia and related podocyte injury. Kidney Int. 2014;86:275–285. 3. Garovic VD, Wagner SJ, Turner ST, et al. Urinary podocyte excretion as a marker for preeclampsia. Am J Obstet Gynecol. 2007;196, 320.e1–7.
4. Munkhaugen J, Vikse BE. New aspects of pre-eclampsia: lessons for the nephrologists. Nephrol Dial Transplant. 2009;24:2964–2967. 5. McDonald SD, Han Z, Walsh MW, et al. Kidney disease after preeclampsia: a systematic review and meta-analysis. Am J Kidney Dis. 2010;55:1026–1039. 6. Vikse BE, Irgens LM, Karumanchi SA, et al. Familial factors in the association between preeclampsia and later ESRD. Clin J Am Soc Nephrol. 2012;7:1819–1826. 7. Wu CC, Chen SH, Ho CH, et al. End-stage renal disease after hypertensive disorders in pregnancy. Am J Obstet Gynecol. 2014;210, 147.e1–8. 8. Paauw ND, Joles JA, Drst JT, et al. High-normal estimated glomerular filtration rate in earlyonset preeclamptic women 10 years postpartum. Hypertension. 2016;68:1407– 1414. 9. Covella B, Vinturache AE, Cabiddu G, et al. A systematic review and meta-analysis indicates long-term risk of chronic and end-stage kidney disease after preeclampsia. Kidney Int. 2019;96:711–727.
Intradialytic nutrition and exercise: convenience versus efficacy T. Alp Ikizler1 Jeong et al. reported the results of a randomized controlled trial in patients on hemodialysis in which intradialytic protein supplementation, with or without exercise, failed to show any beneficial effect on physical function, vascular health, and nutritional markers. These data provide an opportunity to reconsider the appropriate strategy to gain the most benefit from these otherwise proven interventions, that is, prescribing the right intervention for the right patient, at the right dose and at the right time. Kidney International (2019) 96, 549–552; https://doi.org/10.1016/j.kint.2019.04.037 Copyright ª 2019, International Society of Nephrology. Published by Elsevier Inc. All rights reserved.
see clinical trial on page 777
M
uscle wasting and accompanying structural derangements leading to abnormalities in
1 Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
Correspondence: T. Alp Ikizler, Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, 1161 21st Avenue South, S-3223 Medical Center North, Nashville, Tennessee 37232, USA. E-mail: alp. [email protected]
muscle function and physical activity are common in patients with end-stage renal disease, especially in those on maintenance hemodialysis (MHD).1,2 Although the pathophysiology of abnormalities in muscle mass and function is clearly complex, multifactorial, and not fully elucidated, it appears that the common pathway for all the metabolic derangements is related to exaggerated protein degradation relative to protein synthesis along with 549
Is preeclampsia a risk for end-stage renal disease? Claudio Ponticelli1 and Gabriella Moroni2 Little information is available about the risk of end-stage renal disease (ESRD) after preeclampsia. The review of Covella et al. demonstrated that former preeclamptic women have a significant risk of ESRD in the medium term. However, it is still unknown which preeclamptic woman are at higher risk for progressive kidney disease. After delivery, women who had preeclampsia, particularly those with persistent hypertension, symptomatic proteinuria, or microalbuminuria, should receive a regular checkup for kidney disease. Kidney International (2019) 96, 547–549; https://doi.org/10.1016/j.kint.2019.05.009 Copyright ª 2019, International Society of Nephrology. Published by Elsevier Inc. All rights reserved.
see clinical investigation on page 711
T
he placenta is central to the pathogenesis of preeclampsia. During a normal pregnancy, trophoblasts invade the uterus and induce remodeling of the spiral arteries to nourish the fetus, which allows the arteries to settle placental blood flow independent of maternal vasomotor changes. In women with preeclampsia, a defective cytotrophoblast invasion of the uterine spiral arteries occurs. The lumen of these arteries remains narrow and results in poor placental perfusion and hypoxia. Further arrival of blood flow and new oxygen to a hypoxic placenta may create a condition of ischemia-reperfusion that, coupled with maternal susceptibility, leads to the release of reactive oxygen species and anti-angiogenic factors, such as the soluble fms-like protein kinase 1, inflammatory cytokines, and agonistic angiotensin II type-1 receptor autoantibodies. Each of these factors has been shown to induce hypertension experimentally through the production of endothelin-1.1 This potent vasoconstrictor aggravates endothelial lesions by inducing proinflammatory 1 Division of Nephrology Ospedale Maggiore, Milano, Italy (retired); and 2Unita’ Operativa di Nefrologia e Dialisi Fondazione IRCCS Ca’ Granda Ospedale Maggiore di Milano, Italy
Correspondence: Claudio Ponticelli, Ampere 126, 20131 Milano, Italy. E-mail: ponticelli.claudio@ gmail.com Kidney International (2019) 96, 540–554
mechanisms and increases vascular resistance, leading to hypertension. In the glomeruli, the endothelial cells are swollen and demonstrate loss of fenestrations, which allows fibrinoid deposits and accumulation of fluids and lipids, leading to glomerular enlargement and ischemia. This glomerular endotheliosis may result in glomerular dysfunction, podocyturia, and proteinuria.2 Garovic et al.3 first demonstrated that urinary podocyte excretion occurred in patients with preeclampsia. Nephrin and synaptopodin were seen in the urine before proteinuria appeared. The predictive value for the diagnosis of preeclampsia was greater for podocyturia than for any of the measured angiogenic factors. Measures to prevent or attenuate preeclampsia, such as low-dose aspirin, calcium, diet, and lifestyle interventions, showed potential but small benefit. The only measure to cure preeclampsia rests on delivery. However, preterm delivery may result in complications for the newborn, with their incidence and severity being inversely related to the length of pregnancy. In the presence of early preeclampsia (<34 weeks of gestation) or mild hypertension (<160/ 110 mm Hg), treatment may help delay delivery. Preeclampsia management includes oral or intravenous medication to control blood pressure and prevent seizures and steroid injections to speed up the development of the fetal lungs.
However, in cases of intractable hypertension, seizures, thrombocytopenia, coagulopathy, or a syndrome with hemolysis, elevated liver enzymes, and low platelets, delivery should be induced as soon as possible to prevent morbidity and mortality in the mother and fetus. After delivery, blood pressure and proteinuria usually return to pre-pregnancy levels in the mother. For the newborn, prematurity and growth restriction may happen if delivery occurs, respectively, before 37 weeks and 32 weeks. A main problem for the mother is represented by long-term consequences. A concern is the possibility that preeclampsia might lead to permanent kidney damage in women without preexisting chronic kidney disease (CKD). Whether the endothelial lesions that develop during preeclampsia actually reverse after delivery is unknown, because a control kidney biopsy usually is not performed after pregnancy in women with normal renal function. It also is unknown whether soluble fmslike protein kinase 1, inflammatory cytokines, and agonistic angiotensin II type-1 receptor autoantibodies are still altered after delivery.4 On the other hand, microalbuminuria may persist in some women after preeclampsia, which is an indirect sign of persistent vascular and glomerular damage. Thus it would be possible to hypothesize that endothelial dysfunction disrupts the mechanism of vascular homeostasis regulation, predisposing the vessel wall to vasoconstriction, platelet activation, and thrombosis that eventually may result in persisting arterial hypertension and CKD. In addition, a contributory role may be played by podocyturia. The loss of podocytes in urine loss and the reduced expression of nephrin in podocytes recovered from preeclamptic women2,3 may be the index of severe cytoskeleton disorganization, which may result in glomerular and podocyte hypertrophy. If the glomerular growth exceeds the capacity of podocytes to adapt and adequately cover some parts of the filtration surface, podocytes may detach from the glomerular basement membrane. The podocyte loss may lead to glomerular basement membrane denudation and proteinuria, whereas the 547
commentary
Preeclampsia—delivery
Double checkup at 2, 4 and 6 months
Normal blood pressure; neither albuminuria nor podocyturia
Blood pressure ≥ 140/90 mm Hg or proteinuria ≥ 1 g/day
Microalbuminuria and/or podocyturia
No increased risk of CKD and ESRD
Increased risk of CKD and ESRD
Long-term risk of CKD and ESRD
Standard health checkups
Frequent (2–3 months) renal checkups Antihypertensive therapy RAS inhibitors
Renal checkup every year
Figure 1 | Suggested algorithm for women who had preeclampsia. A renal checkup should include at least a clinical visit with a measurement of blood pressure, blood cell count, serum creatinine, estimated glomerular filtration rate, urinalysis with dosage of proteinuria (measured in g/24 h or protein-to-creatinine ratio in spot urine sample), and sediment analysis. If possible, the presence of podocytes should be investigated in cytocentrifuged urine by evaluating the expression of podocalyxin in nucleated or multinucleated cells by immunofluorescence. CKD, chronic kidney disease; ESRD, end-stage renal disease; RAS, renin-angiotensin system.
contact of detached podocytes with Bowman’s capsule can activate parietal epithelial cells that migrate to the glomerular tuft via the denuded glomerular basement membrane. From this entry site, parietal epithelial cells produce extracellular matrix, eventually leading to a focal glomerulosclerosis that may result in proteinuria and CKD. A few years ago, a systematic review of retrospective studies highlighted the association between preeclampsia and persistent postpartum microalbuminuria. This review included 273 women with preeclampsia and 333 women with uncomplicated pregnancies. At a mean of 7.1 years after giving birth, 31% of former preeclamptic women had microalbuminuria compared with 7% of women with uncomplicated pregnancies, a 4-fold increased risk, similar to that of patients with diabetes mellitus type 1. Women with severe preeclampsia had an 8-fold increased risk of microalbuminuria. No difference in serum creatinine or in estimated glomerular filtration rate was seen between women 548
with preeclampsia and control subjects.5 However, criteria of inclusion in the study required a period of at least 6 months after delivery. In many participants, this follow-up period was too short to evaluate the potential risk of CKD and ESRD. After that review, a few long-term studies reported contradictory results. Two large multicenter reports that included patients with follow-up periods of 10 years or more outlined an increased risk of ESRD in women who experienced preeclampsia or hypertensive disorders during pregnancy.6,7 On the other hand, a study that investigated proteinuria and renal function in former preeclamptic women 10 years after giving birth demonstrated only a high-normal estimated glomerular filtration rate and a slightly higher protein excretion.8 To better assess the long-term renal risk of preeclampsia, Covella et al.9 performed a systematic review and a metaanalysis by selecting 21 papers, including 11 meta-analyses, published after 2000. Only papers reporting follow-ups of at least 4 years were selected. The review
reported that the relative risk of ESRD was significantly greater (6.35) in 110,803 women who had preeclampsia in comparison with 2,680,929 control subjects without preeclampsia. The risk of developing albuminuria or CKD increased in preeclamptic women, but the difference with control subjects was not significant. In translating meta-analytic risk into the number of patients with preeclampsia who needed follow-up to detect one adverse event, 310 patients were needed to identify one woman with ESRD. Covella et al.9 should be congratulated for their tremendous efforts in disentangling so many heterogeneous papers. However, they could not elucidate whether the risk of ESRD is related to the presence of underlying diseases that predisposed to the development of preeclampsia or to the severity of preeclampsia or to every form of preeclampsia. Until further data identify patients at high risk for long-term ESRD, we believe that, every 2 months and for at least 6 to 12 months, patients who had preeclampsia should undergo a renal Kidney International (2019) 96, 540–554
commentary
checkup consisting of evaluation of blood pressure, serum creatinine, estimated glomerular filtration rate, microalbuminuria, and urine sediment (including research for podocytes or their components, when possible). CKD is unlikely to develop in women who do not show any renal abnormality after this period. Patients with persistent proteinuria or hypertension after delivery are at risk for ESRD. Those patients should undergo a frequent check of renal parameters and should be treated with antihypertensive drugs, including inhibitors of the renin-angiotensin system in case of proteinuria. The more difficult group is that of asymptomatic women with microalbuminuria. Is this an innocent bystander or an early sign of an endothelial dysfunction that may increase the risk of kidney disease over time? These women should be monitored for long-term periods, but one checkup per year is probably sufficient (Figure 1). Other points remain uncertain. The review included retrospective studies performed in different countries. The criteria for selecting participants and the management of preeclamptic women were probably different. These variables can have influenced the results. The review has the merit of considering patients who had a follow-up of at least 4 years after preeclampsia. Such a period, although longer than those of previous studies, is too short to assess the true risk of ESRD. Finally, it is strange that the risk of ESRD was significantly associated with preeclampsia whereas the risk of CKD was not significantly associated with preeclampsia. One might suspect that many patients with CKD were not diagnosed and treated in due time. However, in spite of these limitations, the message that preeclampsia may represent a risk factor for ESRD is clear and has clinical relevance. In summary, women who experienced preeclampsia are at increased risk of the development of ESRD in the long term. However, retrospective studies, although accurate, cannot identify which patients are at risk of progressive kidney disease. Long-term, prospective studies would be necessary. While waiting for Kidney International (2019) 96, 540–554
solid indications, long-term monitoring of renal parameters is recommended for former preeclamptic women, in particular for those who have persistent hypertension, proteinuria, or even isolated microalbuminuria after delivery. DISCLOSURE All the authors declared no competing interests. REFERENCES 1. George EM, Granger JP. Endothelin key mediator in preeclampsia. Am J Hypertens. 2011;24:964–969. 2. Craici IM, Wagner SJ, Weissgerber TL, et al. Advances in pathophysiology of preeclampsia and related podocyte injury. Kidney Int. 2014;86:275–285. 3. Garovic VD, Wagner SJ, Turner ST, et al. Urinary podocyte excretion as a marker for preeclampsia. Am J Obstet Gynecol. 2007;196, 320.e1–7.
4. Munkhaugen J, Vikse BE. New aspects of pre-eclampsia: lessons for the nephrologists. Nephrol Dial Transplant. 2009;24:2964–2967. 5. McDonald SD, Han Z, Walsh MW, et al. Kidney disease after preeclampsia: a systematic review and meta-analysis. Am J Kidney Dis. 2010;55:1026–1039. 6. Vikse BE, Irgens LM, Karumanchi SA, et al. Familial factors in the association between preeclampsia and later ESRD. Clin J Am Soc Nephrol. 2012;7:1819–1826. 7. Wu CC, Chen SH, Ho CH, et al. End-stage renal disease after hypertensive disorders in pregnancy. Am J Obstet Gynecol. 2014;210, 147.e1–8. 8. Paauw ND, Joles JA, Drst JT, et al. High-normal estimated glomerular filtration rate in earlyonset preeclamptic women 10 years postpartum. Hypertension. 2016;68:1407– 1414. 9. Covella B, Vinturache AE, Cabiddu G, et al. A systematic review and meta-analysis indicates long-term risk of chronic and end-stage kidney disease after preeclampsia. Kidney Int. 2019;96:711–727.
Intradialytic nutrition and exercise: convenience versus efficacy T. Alp Ikizler1 Jeong et al. reported the results of a randomized controlled trial in patients on hemodialysis in which intradialytic protein supplementation, with or without exercise, failed to show any beneficial effect on physical function, vascular health, and nutritional markers. These data provide an opportunity to reconsider the appropriate strategy to gain the most benefit from these otherwise proven interventions, that is, prescribing the right intervention for the right patient, at the right dose and at the right time. Kidney International (2019) 96, 549–552; https://doi.org/10.1016/j.kint.2019.04.037 Copyright ª 2019, International Society of Nephrology. Published by Elsevier Inc. All rights reserved.
see clinical trial on page 777
M
uscle wasting and accompanying structural derangements leading to abnormalities in
1 Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
Correspondence: T. Alp Ikizler, Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, 1161 21st Avenue South, S-3223 Medical Center North, Nashville, Tennessee 37232, USA. E-mail: alp. [email protected]
muscle function and physical activity are common in patients with end-stage renal disease, especially in those on maintenance hemodialysis (MHD).1,2 Although the pathophysiology of abnormalities in muscle mass and function is clearly complex, multifactorial, and not fully elucidated, it appears that the common pathway for all the metabolic derangements is related to exaggerated protein degradation relative to protein synthesis along with 549