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Estimated Glomerular Filtration Rate, Albuminuria, and Adverse Outcomes: An Individual-Participant Data Meta-Analysis.
Writing Group for the CKD Prognosis Consortium; Grams ME, Coresh J, Matsushita K, Ballew SH, Sang Y, Surapaneni A, Alencar de Pinho N, Anderson A, Appel LJ, Ärnlöv J, Azizi F, Bansal N, Bell S, Bilo HJG, Brunskill NJ, Carrero JJ, Chadban S, Chalmers J, Chen J, Ciemins E, Cirillo M, Ebert N, Evans M, Ferreiro A, Fu EL, Fukagawa M, Green JA, Gutierrez OM, Herrington WG, Hwang SJ, Inker LA, Iseki K, Jafar T, Jassal SK, Jha V, Kadota A, Katz R, Köttgen A, Konta T, Kronenberg F, Lee BJ, Lees J, Levin A, Looker HC, Major R, Melzer Cohen C, Mieno M, Miyazaki M, Moranne O, Muraki I, Naimark D, Nitsch D, Oh W, Pena M, Purnell TS, Sabanayagam C, Satoh M, Sawhney S, Schaeffner E, Schöttker B, Shen JI, Shlipak MG, Sinha S, Stengel B, Sumida K, Tonelli M, Valdivielso JM, van Zuilen AD, Visseren FLJ, Wang AY, Wen CP, Wheeler DC, Yatsuya H, Yamagata K, Yang JW, Young A, Zhang H, Zhang L, Levey AS, Gansevoort RT.
Major cardiovascular events and subsequent risk of kidney failure with replacement therapy: a CKD Prognosis Consortium study.
Mark PB, Carrero JJ, Matsushita K, Sang Y, Ballew SH, Grams ME, Coresh J, Surapaneni A, Brunskill NJ, Chalmers J, Chan L, Chang AR, Chinnadurai R, Chodick G, Cirillo M, de Zeeuw D, Evans M, Garg AX, Gutierrez OM, Heerspink HJL, Heine GH, Herrington WG, Ishigami J, Kronenberg F, Lee JY, Levin A, Major RW, Marks A, Nadkarni GN, Naimark DMJ, Nowak C, Rahman M, Sabanayagam C, Sarnak M, Sawhney S, Schneider MP, Shalev V, Shin JI, Siddiqui MK, Stempniewicz N, Sumida K, Valdivielso JM, van den Brand J, Yee-Moon Wang A, Wheeler DC, Zhang L, Visseren FLJ, Stengel B.
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Chronic kidney disease (newly identified): Clinical presentation and diagnostic approach in adults CLINICAL PRESENTATION
CKD patients may present with symptoms and signs resulting directly from diminished kidney function, such as edema or hypertension. However, many have no clinical symptoms, and kidney disease is often detected in these patients when an elevated serum creatinine, reduced estimated glomerular filtration rate (eGFR), or an abnormal urinalysis is discovered incidentally (when such tests are obtained as part of routine evaluation or for a possibly unrelated disorder). In addition, radiographic findings (eg, small and echogenic kidneys [by ultrasound] suggesting chronic damage, multiple bilateral renal cysts with enlarged kidneys suggestive of polycystic kidney disease) may be observed on imaging performed for some other reason.
Depending upon the duration and severity of CKD, patients may also present with symptoms and/or signs of prolonged kidney failure, including weakness and easy fatigability, anorexia, vomiting, pruritus, and, in very advanced stages, with encephalopathy or seizures.
An abnormally reduced urine output (ie, oliguria or anuria) is seldom observed with CKD alone and always indicates at least some component of acute kidney injury (AKI). Oliguria or anuria may be present among patients with AKI superimposed on CKD, such as may be observed in a patient with chronic obstruction who develops acute urinary retention. Similarly, anuria as a result of severe or prolonged shock, bilateral urinary tract obstruction, pregnancy-related cortical necrosis, or bilateral renal arterial occlusion (eg, due to a dissecting aortic aneurysm) may occur in patients with underlying CKD. (See "Evaluation of acute kidney injury among hospitalized adult patients", section on 'Clinical manifestations'.)
Other common laboratory abnormalities that may be part of the clinical picture include anemia, hyperphosphatemia, hyperkalemia, metabolic acidosis, hypocalcemia, and elevated parathyroid hormone (PTH).
COVID-19: Issues related to acute kidney injury, glomerular disease, and hypertension
At the end of 2019, a novel coronavirus (ie, SARS-CoV-2) was identified as the cause of a cluster of pneumonia cases in Wuhan, a city in the Hubei Province of China. By 2020, it led to a pandemic that has spread throughout most countries of the world. SARS-CoV-2 disease (COVID-19) primarily manifests as a lung infection with symptoms ranging from those of a mild upper respiratory infection to severe pneumonia, acute respiratory distress syndrome, and death. COVID-19 disproportionately affects patients with preexisting comorbidities, such as patients with various types of kidney disease.
With the widespread use of vaccinations, availability of antiviral therapy, and the emergence of less pathogenic variants of SARS-CoV-2, many strategies developed to mitigate the effect of COVID-19 on patients with kidney disease are no longer needed. However, it is possible that virulent cases of COVID-19 may surge again in the future. In addition, the response to the COVID-19 pandemic will inform the management of future outbreaks of severe respiratory disease in patients with kidney disease.
Antihypertensive therapy and progression of chronic kidney disease: Experimental studies
Extensive studies in animals and humans have shown that progression of a variety of chronic kidney diseases may be largely due to secondary hemodynamic and metabolic factors, rather than the activity of the underlying disorder. Identification of these factors, such as intraglomerular hypertension and glomerular hypertrophy, is important clinically because they can be treated, possibly preventing or minimizing further glomerular injury [1-3]. A review of the mechanisms by which these alterations might occur and how they might induce glomerular injury is available elsewhere. (See "Secondary factors and progression of chronic kidney disease".)
An important component of this approach is antihypertensive therapy with blockers of the renin angiotensin system (RAS), specifically use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs). The experimental studies supporting this approach will be reviewed here. The clinical trials and recommendations are presented separately. (See "Antihypertensive therapy and progression of nondiabetic chronic kidney disease in adults".)
PREFERENTIAL EFFECT OF RAS BLOCKERS ON RENAL HEMODYNAMICS
From a therapeutic viewpoint, lowering systemic blood pressure is beneficial in a variety of experimental kidney diseases, at least in part by reducing intraglomerular pressure [1,2,4-6]. Renin angiotensin system (RAS) blockers, including angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), appear to be particularly effective in this regard; this effect may be related to reversal of the angiotensin II-induced increase in resistance at the efferent or postglomerular arteriole [4,5]. Dilation of the efferent arteriole will facilitate blood movement out of the glomerulus, lowering the intraglomerular pressure independent of any change in systemic blood pressure. A brief review of the actions of angiotensin II on glomerular hemodynamics is available elsewhere. (See "Renal effects of ACE inhibitors in hypertension".)
It is presumed that the deleterious effect of angiotensin II represents local generation since circulating levels are normal or reduced (due to volume expansion) in many patients with chronic kidney disease . In the remnant kidney model of chronic kidney failure, for example, endothelial injury or activation is associated with enhanced expression of angiotensinogen mRNA, which may then lead to increases in angiotensinogen and angiotensin II production .
Angiotensin receptor blockers — Data in animal models have found that ARBs are as effective as ACE inhibitors [9-13], albeit with a lesser antiproteinuric effect [14,15].
With experimental models, some variability in results may be due to differences in dosing, which was mostly based on the maximal blood pressure reductions. In some experimental studies, much higher levels of the angiotensin-I receptor are noted in kidney parenchyma than in vascular smooth muscle cells . This suggests that higher doses of ARBs may be required to effectively block kidney parenchymal receptors than the doses used to lower blood pressure. These much higher doses may confer effects beyond that obtained with blood pressure lowering, particularly decreased inflammation and superior nephroprotection.
This hypothesis was evaluated in the 5/6 renal ablation model in which conventional doses of losartan (L50), supplemented with hydrochlorothiazide and hydralazine to achieve similar blood pressures, were compared with 10-fold higher doses of losartan (L500) . Among the effects measured, glomerular pressure and glomerular filtration rate were similar with both L50 and L500, although blood pressure and renal vascular resistance were lower with L500. Although kidney injury and albuminuria were partially reduced by L50 at four months postsurgery, L500 completely arrested kidney inflammation and injury and was associated with regression of albuminuria. This finding suggests that full blockade of angiotensin-I receptors requiring much higher doses of ARBs may be associated with maximum nephroprotection.
Human studies show that ACE inhibitors and ARBs have similar benefits on albuminuria and progression of kidney function loss in both diabetic and nondiabetic kidney disease [18-20]. Any noncomparable effects of ACE inhibitors and ARBs may have resulted from variable blood pressure-lowering efficacy of different ARBs [18,21-23]. In addition, real-world evidence from a large observational study (including approximately two million people) found that there was no difference in efficacy of blood pressure control between ACE inhibitors and ARBs, but ARBs were better tolerated . (See "Antihypertensive therapy and progression of nondiabetic chronic kidney disease in adults".)
Other antihypertensive drugs — Other drugs, such as hydralazine, dihydropyridine calcium channel blockers, diuretics, and beta blockers, have not been shown to reverse intraglomerular hypertension (because they do not produce preferential efferent dilatation) and therefore may be less likely to protect against progressive glomerular injury (figure 1) [5,25]. Hydralazine and the dihydropyridine calcium channel blockers (eg, nifedipine, amlodipine), appear to produce prominent afferent or preglomerular arteriolar dilatation [5,6,26,27]. Decreased resistance at this site will allow more of the systemic pressure to be transmitted to the glomerulus, possibly producing no change or even an elevation in intraglomerular pressure, despite the associated reduction in systemic blood pressure. Increased efferent resistance also may occur, as the drug-induced vasodilatation leads to activation of the renin-angiotensin system. In comparison to nifedipine and amlodipine, nondihydropyridine calcium channel blockers (diltiazem and verapamil) are less potent vasodilators and have been shown to decrease the resistance at the efferent arteriole [6,25,28].
Studies using calcium channel blockers in experimental models of kidney disease have revealed conflicting results [6,26]: some have shown increasing proteinuria (consistent with a rise in intraglomerular pressure) and little protection against glomerulosclerosis , while others have shown benefit by mechanisms that may in part be independent of the intraglomerular pressure. (See "Secondary factors and progression of chronic kidney disease".)