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• Nephrotic/Nephritis Management
• From Paediatrics ward
• By Shimelis Engida (PG )

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Presentation outlines

• Introduction
• Epidemiology
• Risk factors Aetiology
• Pathophysiology
• Clinical presentation
• Complications
• Treatment
• Evaluation and monitoring

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Introduction

• The nephrotic syndrome is caused by renal
  diseases that increase the permeability across
  the glomerular filtration barrier.
• Nephrotic range proteinuria -Urinary protein
  excretion greater than 50 mg/kg per day
• Hypoalbuminemia - Serum albumin concentration
  less than 3 g/dL (30 g/L)
• Oedema
• Hyperlipidaemia

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Cont..

• The nephritic syndrome is a clinical syndrome
  that presents as-
• Haematuria
• elevated blood pressure
• decreased urine output, and oedema.
• The major underlying pathology is inflammation of
  the glomerulus that results in nephritic syndrome

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Epidemiology

• As per the final report by the National Center of
  Health Statistics, nephritis syndrome, along with
  nephrotic syndrome, is the 9th leading cause of
  death in the USA in the year 2017.
• The reported number of combined deaths due to the
  nephritic syndrome, nephrotic syndrome, and renal
  diseases was 50,633 out of a total of 2,813,503
  deaths in the year 2017

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Risk factors

• Risk factors of development of minimal change
  disease include
• Children within the Age gt1 year but lt8 years
• Hodgkin lymphoma
• Leukemia
• Recent viral illness
• Toxins such as mercury, gold, bee stings, fire
  coral exposure.
• Medication

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Co

• focal segmental glomerulosclerosis (FSGS)
• Male gender
• Black race
• Family history
• Heroin abuse
• Drugs known to be associated with FSGS
• Chronic viral infection
• Single kidney status
• Obesity
• The following are considered risk factors for the
  development of nephrotic syndrome

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Etiology

• 90 - are primary glomerular abnormality
• Other are involvement of other disease (10)
• We can classify based on etiology
• Primary
• Secondary
• congenital and infantile nephrotic syndrome

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Conti.....

• Based on pathological
• Minimal change disease (MCD)
• Focal segmental glomerulosclerosis (FSGS)
• Membranous glomeruli nephropathy
• Membranoproliferative glomerulonephritis (MPGN)
• Mesangial proliferation
• Focal and global glomerulosclerosis

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Tendencies of Glomerular Diseases to Manifest
Nephrotic and Nephritic Features
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CLASSIFICATION

• Primary nephrotic syndrome, which refers to
  nephrotic syndrome in the absence of an
  identifiable systemic disease.
• Secondary nephrotic syndrome, which refers to
  nephrotic syndrome in the presence of an
  identifiable systemic disease.
• Congenital and infantile nephrotic syndrome,
  which occur in children less than one year of age
  and can be either secondary (mostly due to
  infection) or primary.

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Pathophysiology

• Damaged glomerular capillary membrane
• Increase permeability of glomerular capillary
  wall which leads to massive proteinuria, and
  hypoalbuminemia
• Decrease oncotic pressure
• Generalized edema
• Activation of RAAS
• Sodium retention edema

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Con..
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Clinical presentations

• Nephrotic
• Edema
• Weight gain
• Fatigue
• BP normal/raised
• Leukonychia
• Breathlessness
• Pleural effusion, fluid overload, AKI
• DVT/PE/MI
• Eruptive xanthomata/ xanthalosmata

• Nephritic
• Haematuria (E.g. colacoloured)
• Proteinuria
• Hypertension and edema as renal function declines
• Oliguria
• Flank pain
• General systemic symptoms
• Post-infectious 2-3 weeks after
  strep-throat/URTI

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Complications

• Malnutrition
• Nephrotic edema
• Infection of NS
• Thromboembolic complication
• Lipid abnormality
• Acute renal failure
• Chronic kidney disease

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TREATMENT
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Non-pharmacologic Therapy

• Restriction of sodium intake to 50 to 100 mEq/day
  
• To control edema, hypertension and proteinuria.
• Restriction of protein intake of 0.8 to 1 g/day
• To reduce proteinuria and progression of renal
  disease
• a low-fat diet of lt 200 mg cholesterol/day. Total
  fat should account for lt 30 of daily total
  calories.
• plasmapheresis or plasma exchange, may be used to
  remove the inflammatory mediators

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Pharmacological Treatment

• Initial treatment of NS in children
• We recommend that oral glucocorticoids be given
  for 8 weeks (4 weeks of daily glucocorticoids
  followed by 4 weeks of alternate-day
  glucocorticoids) or 12 weeks (6 weeks of daily
  glucocorticoids followed by 6 weeks of
  alternate-day glucocorticoids) (1B)

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• Immunosuppressive Agents
• are commonly used to alter the immune processes
  that are responsible for several of the
  glomerulonephritides.
• Corticosteroids reduce the production and/or
  release of many substances that mediate the
  inflammatory process
• such as prostaglandins, leukotrienes,platelet-act
  ivating factors, tumor necrosis factors, and
  interleukin-1 (IL-1).
• Cytotoxic agents, such as cyclophosphamide,
  chlorambucil, or azathioprine, are commonly used
  to treat glomerular diseases.

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• The standard dosing regimen for the initial
  treatment of nephrotic syndrome is daily oral
  prednisone/prednisolone 60 mg/m2/d or 2 mg/kg/d
  (maximum 60 mg/d) for 4 weeks followed by
• alternate day prednisone/prednisolone, 40 mg/m2
  or 1.5 mg/kg (maximum of 50 mg) for other 4
  weeks,
• or prednisone/prednisolone 60 mg/m2/d (maximum 60
  mg/d) for 6 weeks followed by alternate day
  prednisone/prednisolone, 40 mg/m2 or 1.5 mg/kg
  (maximum of 50 mg), for other 6 weeks.

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Prevention and treatment of relapses of NS in
children

• For children with frequently relapsing and
  steroid-dependent nephrotic syndrome
• If frequent relapse (2 or more relapses in the
  initial 6 months or more than 3 relapses in any
  12 months),
• prednisolone 60mg/m2 (maximum 80mg) daily until
  urinary protein turns negative or trace for 3
  consecutive days followed by alternate day
  therapy with 0.1-0.5mg/kg for 6 months and then
  taper.

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• For children with frequently relapsing nephrotic
  syndrome who develop serio glucocorticoid-related
  adverse effects and for all children with
  steroid-dependent nephrotic syndrome
• we recommend that glucocorticoid-sparing agents
  be prescribed, rather than no treatment or
  continuation with glucocorticoid treatment alone
  (1B).

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• If infrequent relapse (lt 2 relapses in 6 months
  or lt 3 relapses in one year)
• prednisolone 60mg/m2 (maximum 80mg) daily until
  urinary protein turns negative or trace for 3
  consecutive days followed by alternate day
  therapy with 40mg/m2 (maximum 60mg) for 28 days
  or 14 doses.
• If the child relapses while on alternate day
  prednisolone,
• add levamisole 2.5mg/kg on alternate days for
  6-12 months, then taper prednisolone and continue
  levamisole for 2-3 years.

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Steroid-resistant nephrotic syndrome in children

• We recommend using cyclosporine or tacrolimus as
  initial second-line therapy for children with
  steroid-resistant nephrotic syndrome (1C).

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• Management of complication

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Diuretics

• Management of nephrotic edema involves salt
  restriction, bed rest, and use of support
  stockings and diuretics.
• Large doses (160 to 480 mg of furosemide)may be
  needed for patients with moderate edema.
• presence of large amounts of protein in the urine
  promotes drug binding, and thereby reduces the
  availability of the diuretic to the luminal
  receptor sites.
• reduced sodium delivery to the distal tubule
  secondary to decreased glomerular perfusion may
  also alter diuretic effectiveness.
• thiazide diuretic or metolazone may be added to
  enhance natriuresis.

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Cont

• Alternatively, continuous IV infusion of a loop
  diuretic, such as furosemide 160 to 480 mg/day,
  may be employed.
• For patients with morbid edema, albumin infusion
  may be used to expand plasma volume and increase
  diuretic delivery to the renal tubules
• However, it may precipitate CHF and may
  alsoreduce therapeutic response to steroids in
  patients with minimal-change nephropathy.
• For patients with significant edema, the goal of
  treatment should be
• a daily loss of 1 to 2 lb (0.45-0.9 kg) of fluid
  until the patients desired weight has been
  obtained.

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Antihypertensive Agents

• Optimal control of hypertension for patients with
  glomerular disease is important in reducing both
  the progression of renal disease and the risk for
  cardiovascular
• According to JNC 8 guidelines, the target BP for
  patients with CKD (GFRlt 60 mL/min/1.73 m2 is lt
  140/90 mmHg
• ACEIs ARBs delay the loss of renal function for
  patients with diabetic and nondiabetic (primarily
  glomerulonephritis)renal diseases.
• Non-dihydropyridine calcium channel blockers (eg,
  diltiazem and verapamil) reduce proteinuria and
  preserve renal function and could be used as an
  additional agent.

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Antiproteinuria Agents

• ACEIs ARBs
• The antiproteinuric effect of ACEIs is associated
  with a fall in filtration fraction, suggesting a
  reduction in intraglomerular pressure.
• ACEIs and ARBs may also have direct effects on
  podocytes, resulting in reduction of proteinuria
  and glomerular scarring.
• ACEI inhibition may also reduce the effect of
  angiotensin II on renal cell proliferation,
  thereby reducing sclerosis.
• ACEIs ARBs can reduce proteinuria through
  differentmechanisms and combined use has been
  shown to be more effective than monotherapy.
• However, the risk of combination therapy has
  become a concern recently.

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Antiproteinuria Agents

• NSAIDs probably reduce proteinuria through PG E2
  inhibition, resulting in a reduction of
  intraglomerular pressure
• Indomethacin and meclofenamate, the two most
  evaluated NSAIDs have similar efficacy to ACEIs,
  and combined
• treatment with an ACEI results in
  additionalproteinuria reduction.
• Adherence to a low-sodium diet or concurrent use
  of a diuretic is needed to maximize the
  antiproteinuric effect.
• Because of their potential for nephrotoxicity,
  especiallyfor patients with preexisting CKD

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Statins

• (HMG-CoA) reductase inhibitors, also known as
  statins
• such as lovastatin, pravastatin, simvastatin,
  fluvastatin atorvastatin and rosuvastatin,
• statins should be used to treat the dyslipidemia
• Aside from the lipid-lowering effects, statins
  can reduce cardiovascular risk independent of
  serum lipid concentrations.
• Meta-analysis of published studies showed that
  statins appear to reduce renal function decline
  andslow the progression of proteinuria
  moderately.
• The beneficial effect may be dose-related
  andduration-dependent

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Anticoagulants

• Renal vein thrombosis andpulmonary emboli are
  serious and common complications of nephrotic
  syndrome,
• patients who have documented thromboembolic
  episodes should beanticoagulated with warfarin
  until remission of nephrotic syndrome,
• The use of prophylactic anticoagulation is
  controversial.
• A decision analysis study suggested that
  prophylactic anticoagulation is beneficial for
  patients with membranous nephropathy.
• Prophylactic anticoagulation is recommended for
  pts at high risk (ie, those with severe
  nephrotic syndrome and a serum albumin
  concentration less than 2-2.5.

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Monitoring Parameters

• Renal function
• Serum creatinine concentration
• 24-h urine collection for creatinine clearance
  determination
• 24-h urine collection for urinary protein
  excretion
• Urine protein-to-creatinine ratio
• Clinical signs and symptoms
• Nephrotic syndrome
• Protein
• uriaSerum lipid concentrations
• Edema

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• Nephritic presentations
• Hematuria
• Urinalysis
• Complete blood count
• Blood pressure
• General well-being appetite, energy levelKidney
  biopsy to assess disease progression and response
  to therapy
• Assessment of drug therapy adverse reactions and
  toxicities

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Reference

• Heron M. Deaths Leading Causes for 2017. Natl
  Vital Stat Rep. 2019 Jun68(6)1-77. PubMed