In most cases, acute glomerulonephritis progresses to chronic glomerulonephritis, a disorder characterized by irreversible and progressive fibrosis of the glomeruli and tubulointerstitial tissue. This progresses to a progressive reduction in GFR with an accumulation of uremic toxins. The disorder progresses to CKD, ESRD, and finally cardiovascular disease if not managed appropriately. Chronic glomerulonephritis is the third leading cause of CKD and accounts for about 10% of all dialysis patients. 

The National Kidney Foundation defines CKD based on either laboratory findings of kidney damage, including abnormal findings on urinalysis tests or imaging studies or a GFR of less than 60 mL/min maintained for three or more months. NKF classifies progression of renal disease into five stages, from preserved kidney function to end-stage kidney failure. Treatment at each stage is directed toward diagnosis, management, treatment of comorbid conditions, slowing the progression of the disease, and reduction of cardiovascular risk. 

The prognosis depends upon the type of chronic glomerulonephritis, though most lead to ESRD and end in death if renal replacement therapy is not offered. 

The cause of the disease is unknown. It is the third major cause of ESRD (end-stage renal disease) now in the United States and accounts for 10% of all. 

In Japan and most other Asian nations, chronic glomerulonephritis at one point constituted as much as 40% of patients on dialysis. However, based on more current studies, the prevalence of chronic glomerulonephritis in dialysis patients in Japan has dropped to 28%. The reason for this decline is not entirely understood. Over that same period, diabetic nephropathy increased and currently accounts for as many as 40% of patients undergoing dialysis in these same regions. 

An initial injury to nephrons decreases GFR, leading to hypertrophy and hyperfiltration in residual nephrons, including intraglomerular hypertension. The latter adaptive mechanisms tend to preserve GFR and decrease the functional effect of lost nephrons but bring about progressive glomerulosclerosis and further reduction in nephron mass. 

At the earliest stages of renal disease, there is a drastic fall in GFR that may result in an increase in serum creatinine. This elevates creatinine levels in the blood, thus reducing the production of erythropoietin and vitamin D. It also causes the poor excretion of water, potassium, salt, and acids, and finally, platelet dysfunction. Uremia corresponds to a much reduced GFR of approximately 10 mL/min, but its symptomatology can be considered as resulting from the accumulation of certain toxins like phenols, creatinine, guanidines, and BUN. Uremia or Azotemia occurs with a reduction in GFR to less than 60-70 mL/min and is characterized by hypertension, anemia, renal osteodystrophy, hyperphosphatemia, acidosis, hyperkalemia, edema, and hypocalcemia. 

The progression to chronic glomerulonephritis from acute glomerulonephritis varies significantly based on the underlying cause. While patients with poststreptococcal glomerulonephritis typically experience complete recovery of renal function, other forms of glomerulonephritis such as IgA (immunoglobulin A) nephropathy, often follow a more benign course and may not advance to ESRD. The patterns of progression can be summarized as follows: 

1. Focal segmental glomerulosclerosis- Approximately 80% of patients advance to ESRD within 10 years. Those with the collapsing variant of focal segmental glomerulosclerosis, also known as malignant focal segmental glomerulosclerosis, experience a more rapid progression. This variant may be associated with HIV infection or idiopathic. 
2. Membranoproliferative glomerulonephritis- Approximately 40% of patients with this condition progress to ESRD (End-stage renal disease) or CRF (chronic renal failure) within 10 years. 
3. Membranous nephropathy- Approximately 20-30% of patients suffering from this condition develop to CRF (chronic renal failure) or ESRD within 10 years. 
4. Crescentic glomerulonephritis- Almost 90% of patients progress to ESRD within a few weeks or months. 
5. Lupus nephritis- On the whole, around 20% of lupus nephritis patients have progression to chronic renal failure or end-stage renal disease within 10 years. Some histologic variants, such as type IV, may run a more rapid course. Moreover, the presence of antineutrophil cytoplasmic antibodies is an independent risk factor for poor renal outcome. 
6. Poststreptococcal glomerulonephritis- Approximately 1-2% of patients with poststreptococcal glomerulonephritis progress to chronic renal failure (CRF) or end-stage renal disease (ESRD). The risk is particularly high for older children who present with crescentic glomerulonephritis. 

GN prognosis differs with type and degree of severity. Acute GN can be temporary or reversible most of the time if it is diagnosed early. In contrast, chronic GN can go on to decreased kidney function, chronic kidney failure, and end-stage renal disease. Treatment given early can avoid kidney failure; in advanced cases, this may include dialysis or even kidney transplantation. Some mild cases resolve on treatment, but some others improve spontaneously. 

The initial history should focus on identifying the cause and specific symptoms to pinpoint the source of CKD if it is not already known. Identifying these symptoms helps to guide the planning of further diagnosis and management of disease. The next step is to assess for symptoms associated with uremia to determine whether renal replacement is necessary. 

The following indicate uremia: 

1. Pruritis 
2. Change in sensation of taste 
3. Tremors 
4. Peripheral neuropathy 
5. Seizures 
6. Weakness 
7. Fatigue 
8. Vomiting and nausea in the early morning 
9. Loss of appetite 
10. Sleep pattern reversal 

Hypertension and edema are suggestive signs of volume retention. Positional chest pain or dyspnea may indicate pericarditis and fluid overload, respectively. Leg cramps could be an indication of hypocalcemia or other electrolyte imbalances. Fatigue, lethargy, or weakness, lethargy can also results from anemia. 

Observations in the physical examination related to uremia include: 

1. Pulmonary rales 
2. Asterixis 
3. Reduced sensation 
4. Pericardial abrasion in case of pericarditis 
5. Hypertension 
6. Tenderness in epigastric region 
7. Distenion of jugular vein 

1. Uremic neuropathy 
2. Hyperkalemia 
3. Metabolic acidosis 
4. Pericarditis 
5. Pulmonary edema 
6. Uremic encephalopathy 
7. Hypocalcemia 
8. Severe anemia 
9. Uremic GI bleeding 

Approach considerations: 

Close surveillance is required in patients with CKD to diagnose and treat AKI as early as possible. Nephrotoxic agents must be tailored according to the severity of CKD and administered only if the anticipated benefits outweigh the risks. Aggressive management of diabetes, hypertension, and proteinuria and consideration of weight reduction and bariatric surgery may slow progression to ESRD. Specific treatment of glomerular diseases, anemia, renal osteodystrophy, and comorbid conditions needs to be applied. Avoid steroid therapy to prevent complications. 

Pharmacologic therapy 

The control of blood pressure is required in individuals who have more or less than 1 g/day of proteinuria. ACEIs are generally prescribed to lower the blood pressure in CKD patients. ACEIs decrease proteinuria by decreasing efferent arteriolar tone, thereby decreasing intraglomerular hypertension. They are more effective, compared with conventional therapy, in slowing a decline in GFR in both diabetic and nondiabetic proteinuric nephropathies. 

ACEIs combined with ARBs have the potential to provide better blood pressure control along with preservation of renal function compared with either of these medications alone. However, such combination therapy can increase the risk of developing adverse effects like hyperkalemia, deterioration of kidney function, and increased mortality. Diuretics are often required to manage the decreased free-water clearance, and larger doses may be needed to control edema and hypertension when GFR falls below 25 mL/min. 

Other medications to attain target blood pressure include beta blockers, calcium channel blockers, central alpha-2 agonists, alpha-1 antagonists, direct vasodilators, and new classes of antihypertensives which have been shown to be effective: SGLT2i, inhibitors of fibrosis, mineralocorticoid antagonists, sodium bicarbonate, bardoxolone, and direct renin inhibitors. 

For renal osteodystrophy, early replacement with vitamin D is indicated, along with phosphate binders. Nonuremic causes of anemia, like iron deficiency, should be addressed before embarking on erythropoietin therapy. Hyperlipidemia should also be managed to reduce cardiovascular risks, though the benefits associated with lipid lowering toward renal protection are still unclear. 

Nephrology

Lifestyle adjustments:  

To manage edema and hypertension, reduce salt and protein intake, control phosphorous and potassium levels, ensure adequate intake of calcium and Vitamin D and implement weight loss strategies to reduce workload on kidneys and improve overall health. 

Medication management: 

Utilize medications like ARBs, ACE inhibitors, and antihypertensives to manage blood pressure, diuretics to manage fluid retention, and additional agents to achieve target blood pressure and manage symptoms. 

Regular monitoring: 

Regularly monitor kidney function, track blood pressure, electrolyte levels, and fluid overload. Involve nephrologists for tailored treatment plans and complex cases, especially if ESRD progresses. 

Management of comorbid conditions: 

Manage diabetes, hyperlipidemia, and manage anemia by aggressively managing blood glucose levels, addressing high cholesterol and treating underlying causes like iron deficiency before initiating erythropoiesis- stimulating agents. 

Nephrology

Enalapril: It is a competitive inhibitor of Angiotensin converting enzyme. It acts by reducing the levels of angiotensin II thereby reducing the secretion of aldosterone. It also reduces the glomerular protein filtration and intraglomerular pressure. 

Captopril: It is a potent vasoconstrictor which is known to prevent conversion to angiotensin II from angiotensin I, which results in lowering the secretion of aldosterone. 

Benazepril: This is known to prevent the conversion from angiotensin I to II. It increases the concentration of renin in plasma which thereby reduces the secretion of aldosterone. 

Quinapril: It is a competitive inhibitor of ACE which reduces the levels of angiotensin II and lowers the secretion of aldosterone. 

Nephrology

Furosemide: It elevates water excretion via interfering with chloride-binding cotransport system. 

Bumetanide: It raises the water excretion by interfering with chloride-binding cotransport system. 

Ethacrynic acid: This drug is used in refractory cases and indicated in treating edema temporarily. 

Nephrology

Metolazone: It is indicated in treating CHF. It is known to enhance the excretion of potassium, sodium, hydrogen ions and water via inhibition of reabsorption of sodium in distal tubule. 

Hydrochlorothiazide: It causes an increase in the excretion of water, sodium, hydrogen ions and potassium. 

Nephrology

Amlodipine: It acts by blocking slow calcium channels which causes smooth muscle relaxation. 

Nifedipine: It relaxes the coronary smooth muscle thereby producing coronary vasodilation which further improves the myocardial oxygen delivery. 

Verapamil: Calcium ions are inhibited from entering voltage-sensitive and slow channel areas of myocardium and vascular smooth muscles during the phase of depolarization. 

Diltiazem: It inhibits the entry of calcium ions from entering voltage-sensitive areas and slow channels areas of myocardium and vascular smooth muscle. 

Nephrology

Metoprolol: It is a selective β1-adrenergic blocker which reduces the contraction automaticity. 

Bisoprolol: It is a selective blocker of β1-adrenergic receptor which reduces the contraction automaticity. 

Nephrology

Propranolol: It is a non-selective blocker of beta-adrenergic receptor which belongs to class II antiarrhythmics. 

Sotalol: It is a class III antiarrhythmic drug which blocks the potassium ion channels and prolongs the duration of action potential and lengthens QT intervals.  

Labetolol: It is known to block α, β1, and β2 sites of adrenergic receptors and reduce blood pressure. 

Penbutolol: It has slight intrinsic sympathomimetic effects and negative ionotropic and chronotropic effects. 

Nephrology

Doxazosin: It is a selective antagonist of alpha1 adrenergic receptor and belong the class of quinazolines. It causes the vasodilation of arterioles and veins and reduces the blood pressure and total peripheral resistance. 

Terazosin: It reduces the arterial tone by causing blockade of peripheral post synapse. 

Nephrology

Minoxidil: It causes relaxation of arteriolar smooth muscle causing vasodilation. 

Hydralazine: It reduces the systemic resistance by causing arteriolar vasodilation. 

Sodium nitroprusside: It causes vasodilation and ehnces the inotropic effects of heart. 

Nitroglycerin: It works primarily as a venodialtor which reduces both afterload and preload. 

Nephrology

Clonidine: This is known to stimulate the presynaptic alpha2 receptors and further reduces the release of norepinephrine and peripheral vasoconstriction. 

Nephrology

SGLT2 inhibitors diminish glucose absorption in the proximal tubules. In addition, they indirectly inhibit sodium absorption by inhibiting the sodium-hydrogen exchanger. There are several classes of these agents. Caution should be exercised with patients at risk of hypotension, urinary tract infections, diabetic ketoacidosis, and peripheral vascular disease. 

Nephrology

Finerenone: These drugs, as a class, block the action of mineralocorticoids, aldosterone, on its receptors, producing minimal or no hyperkalemia. This causes a decrease in fluid volume and decreases fibrosis associated with aldosterone action.  

Nephrology

Irbesatran: It is known to inhibit the vasoconstrictor and angiotensin II aldosterone secreting effects. 

Valsartan: It is known to block the binding of angiotensin II which lowers the blood pressure and blocks the vasoconstrictor effects. 

Candesartan: It prevents the binding to angiotensin II. 

Nephrology

Chronic glomerulonephritis is a kidney disease that requires systematic management. Diagnosis of the disease was made on full evaluation, including the patient’s history, physical examination, and diagnostic studies. The severity of the disease is based on GFR, proteinuria, and symptoms. The cause is identified, and then primarily the conditions that have resulted in the disease are managed, be it an autoimmune disease, infections, or some other systemic condition. The risk factors are managed through medications and lifestyle modifications. The symptoms are managed through control of blood pressure, management of proteinuria, fluid, and electrolyte balance. As the treatment has to be individualized to slow down the progress of damage to the kidneys, so modifications to lifestyle are advised. The complications are managed through anemia, bone mineral disorders, and cardiovascular risk. The renal replacement therapy is prepared by assessing the need for dialysis or kidney transplantation and planning for it. The patients are followed up regularly, and education on their treatment is provided. Supportive care may be psychosocial, keeping the mental and emotional status in check, or palliative for advanced stages of this chronic condition. Full working through these phases by healthcare providers can provide an integrated approach to the management of chronic glomerulonephritis for their patients, improving outcome and quality of life.