Glomerular Diseases¶
Chapter 326 | Harrison's 22e · Part 9 – Renal & Urinary Tract Disorders
Detailed clinical reference synthesised from Harrison's Principles of Internal Medicine, 22nd Edition
🔑 Key Clinical Points¶
- See source text for full details
📑 Table of Contents¶
📋 Figures in This Chapter¶
| # | Type | Description |
|---|---|---|
| 1 | 🖼 Figure | Glomerular architecture |
| 2 | 🖼 Figure | Figure / Illustration |
| 3 | 🖼 Figure | The glomerulus is injured by a variety of mechanisms |
| 4 | 🖼 Figure | The glomerulus is injured by a variety of mechanisms |
RAW CONTENT¶
[PAGE 2411] Glomerular Diseases 2411 CHAPTER 326 population at large, and this is particularly true of diabetic patients. Kotton CN et al: The third international consensus guidelines on Contributing factors are the use of glucocorticoids and sirolimus, the management of cytomegalovirus in solid-organ transplantation. as well as hypertension. Recipients of renal transplants have a high Transplantation 102:900, 2018. prevalence of coronary artery and peripheral vascular diseases. The Lentine KL et al: OPTN/SRTR 2021 Annual data report: Kidney. Am percentage of deaths from these causes has been slowly rising as the J Transplant 23:21, 2023. numbers of transplanted diabetic patients and the average age of recipi- Loupy A et al: Complement-binding anti-HLA antibodies and kidney- ents increase. More than 30% of kidney transplant recipient mortality is allograft survival. N Engl J Med 369:1215, 2013. attributable to cardiovascular disease. Strict control of blood pressure Orandi BJ et al: Survival benefit with kidney transplants from HLA- and blood sugar and lipid levels is essential in this population. incompatible live donors. N Engl J Med 374:940, 2016. Hypertension may be caused by (1) native kidney disease, (2) rejec- tion activity in the transplant, (3) renal artery stenosis if an end-to-end anastomosis was constructed with an iliac artery branch, and (4) renal CNI toxicity, which may improve with reduction in dose. Calcium 326 Glomerular Diseases channel blockers are shown to improve long-term mortality. Ameliora- tion of hypertension to the range of 120–130/70–80 mmHg should be the goal in all patients. Julia B. Lewis, Eric G. Neilson Hypercalcemia after transplantation may indicate failure of hyper- plastic parathyroid glands to regress. Aseptic necrosis of the head of the femur when it occurs is probably due to preexisting hyperparathy- Two human kidneys harbor nearly 1.8 million glomerular capillary roidism, with aggravation by glucocorticoid treatment. With improved tufts. Each glomerular tuft resides within Bowman’s space. The cap- management of calcium and phosphorus metabolism during chronic sule circumscribing this space is lined by parietal epithelial cells that dialysis, the incidence of parathyroid-related complications has fallen transition into tubular epithelia forming the proximal nephron or dramatically. Persistent hyperparathyroid activity may require subtotal migrate into the tuft to replenish podocytes. The glomerular capillary parathyroidectomy. tuft derives from an afferent arteriole that forms a branching capil- Although most transplant patients have robust production of eryth- lary bed embedded in mesangial matrix (Fig. 326-1). This capillary ropoietin and normalization of hemoglobin, anemia is commonly network funnels into an efferent arteriole, which passes filtered blood seen in the posttransplant period. Often the anemia is attributable into cortical peritubular capillaries or medullary vasa recta that supply to bone marrow–suppressant immunosuppressive medications such and exchange with a folded tubular architecture. Hence, the glomerular as azathioprine, mycophenolic acid, and mTOR inhibitors. Gastroin- capillary tuft, fed and drained by arterioles, represents an arteriolar testinal bleeding is a common side effect of high-dose and long-term portal system. Fenestrated endothelial cells resting on a glomerular steroid administration. Many transplant patients have creatinine basement membrane (GBM) line glomerular capillaries. Delicate foot clearances of 30–50 mL/min and can be considered to have chronic processes extending from epithelial podocytes shroud the outer surface renal insufficiency for anemia management, including supplemental of these capillaries, and adjacent podocytes interconnect to each other erythropoietin. by slit-pore membranes forming a selective filtration barrier. Chronic hepatitis, particularly when due to hepatitis B virus, can be The glomerular capillaries filter 120–180 L/d of plasma water con- a progressive, fatal disease over a decade or so. Patients who are persis- taining various solutes for reclamation or discharge by downstream tently hepatitis B surface antigen–positive are at higher risk, according tubules. Most large proteins and all cells are excluded from filtration to some studies, but the presence of HCV is also a concern when one by a physicochemical barrier governed by pore size and negative elec- embarks on a course of immunosuppression in a transplant recipient. trostatic charge. The mechanics of filtration and reclamation are quite However, the introduction of the new highly effective, direct-acting complicated for many solutes (Chap. 320). For example, in the case of HCV antiviral medications reduced this risk significantly. serum albumin, the glomerulus is an imperfect barrier. Although albu- In conclusion, while kidney transplantation has progressed sig- min has a negative charge, which would tend to repel the negatively nificantly toward the goals of longer patient survival and better qual- charged GBM, it only has a physical radius of 3.6 nm, while pores in the ity of life, the field still has significant challenges and unmet needs. GBM and slit-pore membranes have a radius of 4 nm. Consequently, Advanced immunologic and genetic studies have led and will continue variable amounts of albumin inevitably cross the filtration barrier to to lead us to detailed understanding of alloimmunity at the molecular be reclaimed by megalin and cubilin receptors along the proximal level. Noninvasive biomarkers for monitoring and diagnosing rejection tubule. Remarkably, humans with normal nephrons excrete on average and novel therapeutic targets will continue to evolve. Further effort 8–10 mg of albumin in daily voided urine, ~20–60% of total excreted is needed to achieve equity and improve personalized care of kidney protein. This amount of albumin, and other proteins, can rise to gram transplant recipients. quantities following glomerular injury. The breadth of diseases affecting the glomerulus is expansive ■ FURTHER READING because the microenvironment supporting the glomerular capillaries Allen PJ et al: Recurrent glomerulonephritis after kidney transplanta- can be injured in a variety of ways, producing many different lesions. tion: Risk factors and allograft outcomes. Kidney Int 92:461, 2017. Some order to this vast subject is brought by grouping all of these dis- Chadban SJ et al: Summary of the Kidney Disease: Improving Global eases into a smaller number of clinical syndromes. Outcomes (KDIGO) clinical practice guideline on the evaluation and management of candidates for kidney transplantation. Transplanta- PATHOGENESIS OF GLOMERULAR DISEASE tion 104:708, 2020. There are many forms of glomerular disease with pathogenesis variably Chapman JR et al: Cancer in the transplant recipient. Cold Spring linked to the presence of genetic mutations, infection, toxin exposure, Harb Perspect Med 3:pii:a015677, 2013. autoimmunity, atherosclerosis, hypertension, emboli, thrombosis, or Euvrard S et al: Sirolimus and secondary skin-cancer prevention in diabetes mellitus. Even after careful study, however, the cause often kidney transplantation. N Engl J Med 367:329, 2012. remains unknown, and the lesion is called idiopathic. Specific or Grams ME et al: Kidney-failure risk projection for the living kidney- unique features of pathogenesis are mentioned with the description of donor candidate. N Engl J Med 374:411, 2016. each of the glomerular diseases later in this chapter. Hariharan S et al: Long-term survival after kidney transplantation. Some glomerular diseases result from genetic mutations producing N Eng J Med 385:729, 2021. familial disease or a founder effect: congenital nephrotic syndrome Hirsh HH et al: BK polyomavirus in solid organ transplantation: from mutations in NPHS1 (nephrin) and NPHS2 (podocin) affects Guidelines from the American Society of Transplantation Infectious the slit-po
Figures & Illustrations¶
Reproduced from Harrison's 22nd Edition.
Figure 1¶
Caption: FIGURE 326-1 Glomerular architecture. A. The glomerular capillaries form from a capillary bed (tuft), and a draining efferent arteriole. (From VH Gattone II et al: surface of the glomerular capillaries (arrow shows foot process). C. Scanning electron various normal regions of the glomerulus on light microscopy. (A–C: Courtesy of Dr. polymorphisms in the gene encoding apolipoprotein L1, APOL1, are a major risk for nearly 70% of African Americans with nondiabetic end-stage kidney disease (ESKD), particularly FSGS; monogenetic causes of FSGS are increasingly linked to early age of onset and to genes encoding type IV collagen in older adults, suggesting that much of
Figure 2¶
Caption: Figure 2
Figure 3¶
Caption: FIGURE 326-2 The glomerulus is injured by a variety of mechanisms. A. Preformed basement membrane (GBM) in the subendothelial space or can form in situ along the IgG demonstrating linear staining from a patient with anti-GBM disease or immune glomerular injury have a complicated pathogenesis. Immune deposits and complement T lymphocytes may follow to participate in the injury pattern as well. D. Amplification depending on the location of the target antigen and the genetic polymorphisms of the proliferation.
Figure 4¶
Caption: FIGURE 326-2 The glomerulus is injured by a variety of mechanisms. A. Preformed basement membrane (GBM) in the subendothelial space or can form in situ along the IgG demonstrating linear staining from a patient with anti-GBM disease or immune glomerular injury have a complicated pathogenesis. Immune deposits and complement T lymphocytes may follow to participate in the injury pattern as well. D. Amplification depending on the location of the target antigen and the genetic polymorphisms of the proliferation.
Generated from Harrison's Principles of Internal Medicine, 22nd Edition.