• Rachel Cason MD, Priyadarshini John DM, Swasti Chaturvedi MBBS, MD, FRACP

Nephrectomy: When We Need to Say Goodbye

Updated: Nov 1

Written by - Rachel Cason, MD; Priyadarshini John, DM; Swasti Chaturvedi, MBBS, MD (pediatrics), FRACP

Infographics: Salar Bani-Hani, MD; Priyadarshini John, DM


AcademicCME (www.academiccme.com) is accrediting this educational activity for CE and CME for clinician learners. Please go to https://academiccme.com/kicr_blogposts/ to claim credit for participation.

INTRODUCTION:

As nephrologists, our primary goal is to preserve kidney function for as long as possible. However, there are circumstances when kidneys do not behave as they should, and nephrectomy is more beneficial than leaving a dysfunctional kidney. Nephrectomy can be broadly classified into native kidney nephrectomy or transplant kidney nephrectomy (aka allograft nephrectomy). Figure 1 below outlines indications for nephrectomy.


Figure 1. Indications for Native kidney nephrectomy.


Native Kidney Nephrectomy

Once indicated, there are several approaches to nephrectomy:

  • Surgical nephrectomy

  • Renal artery embolization

  • Ureteral ligation

  • Medical nephrectomy (MN)

Non-medical Nephrectomy


1. Surgical nephrectomy can be

  • Total (radical) or partial (nephron-sparing): Radical nephrectomy involves removing the ENTIRE kidney, ureter, adrenal gland, surrounding lymph nodes, and fatty tissue. Partial nephrectomy of a kidney with Wilms tumor carries better outcomes with negligible risks than total nephrectomy.

  • Unilateral or bilateral nephrectomy. Indications for bilateral nephrectomy include autosomal recessive polycystic kidney disease (ARPKD) and autosomal dominant polycystic kidney disease (ADPKD) owing to their large sizes. Indications for unilateral nephrectomy include unilateral tumors, living kidney donation, severe unilateral kidney trauma, recurrent pyelonephritis in a refluxing non- or minimally-functioning kidney, atrophic kidney, and in the setting of a non-functioning, dysplastic kidney resulting in severe hypertension (HTN).

  • Sequential nephrectomy: A scenario encountered in pediatric nephrology is Congenital Nephrotic Syndrome, which presents before three months of age. Congenital Finnish-type nephrotic syndrome is characterized by massive proteinuria, and treatment often involves daily albumin infusions, intensified nutrition, and initial therapy with NSAID and renin-Angiotension-Aldosterone system inhibition (RAASi), thereby reducing proteinuria (aka medical nephrectomy, discussed later). This is followed by bilateral nephrectomy and subsequent kidney transplant at the age of 1-2 years. However, there are times when unilateral nephrectomy is undertaken initially to reduce proteinuria while simultaneously preserving residual kidney function. The child may undergo removal of the remaining kidney at a later stage; a process termed sequential nephrectomy. Removing one kidney at a time helps reduce proteinuria and fluid management while preserving residual kidney function, so the child is not immediately made dialysis dependent. Sequential nephrectomy is also sometimes done in severe treatment-resistant nephrotic syndrome in an older child.

  • Currently, nephrectomies are not performed with Multicystic Dysplastic Kidneys (MCDK). Studies have shown that there is no increased risk for the development of malignancy or long-term HTN.

  • Surgical nephrectomies can be open, laparoscopic, or robot-assisted.

2. Renal artery embolization (RAE) has been described for cases of severe nephrotic syndrome (NS), renal masses at risk for hemorrhage with resection (i.e., tuberous sclerosis-associated angiomyolipomas), and acute renal hemorrhage associated with trauma.


Figure 2 shows before and after embolization with hydrogel (A and B). Panel E of Figure 1 shows 3D modeling demonstrating kidney atrophy after embolization.


Figure 2:



3. Ureteral ligation has been described in patients with poor health status secondary to resistant severe proteinuria. It has also been used before kidney transplantation (KT) as an alternative to surgical nephrectomy. Specifically in children, a unilateral ligation approach was compared to unilateral surgical nephrectomy before KT (indications for which included polyuria, massive resistant proteinuria, intractable HTN, and recurrent kidney infection). The benefits of ureteral ligation over surgical nephrectomy include a less invasive procedure with smaller incisions and less risk for bleeding. Specifics of the ureteral ligation technique are beyond the scope of this blog; however, it has been described via hand-assisted laparoscopic and open methods with ligation at the ureteropelvic junction.


4. Medical Nephrectomy (MN): Medical nephrectomy uses medicines to decrease kidney function (i.e., lower the GFR). The main advantage is that MN is less invasive and avoids complications related to surgery and anesthesia, although that does not mean it is without risk. Indications for MN include severe treatment-resistant nephrotic syndrome (NS), congenital NS with severe proteinuria, and to induce oliguria or decrease proteinuria in kidney failure (KF) on dialysis in preparation for the transplant. Severe symptomatic NS leads to fluid overload, hypercoagulable states, malnutrition, and risk of atherosclerosis in older age groups. In this scenario, a medical nephrectomy is used to reduce proteinuria. Other indications for MN include tubular disorders such as Bartter syndrome and diabetes insipidus to reduce excessive electrolyte and fluid losses by reducing GFR. Enjoy the interesting Twitter discussion on MN from nephrologists worldwide on indications.


What medications can be used to perform a medical nephrectomy? There are a few good options, we will discuss each. Some sources also report using combinations of these drugs.


Figure 3 Medial nephrectomy agents and mechanism of activity.

Renin-Angiotensin-Aldosterone System Inhibition (RAASi) with angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II (AngII) receptor blockers (ARB). Due to their easy availability and inexpensive nature, this class is often used to decrease proteinuria in patients with nephrotic syndrome (particularly Focal Segmental Glomerulosclerosis-FSGS), diabetic nephropathy, or other proteinuric diseases.


ACEi inhibits the production of AngII, which is increased in states of apparent volume depletion due to RAAS activation. Ang II inhibition leads to decreased vasoconstriction of the efferent arteriole, lowering intraglomerular pressure. AngII is also a growth factor contributing to cellular hypertrophy in the heart and kidney, as well as glomerulosclerosis. The mechanism of action (MOA) of an ARB blocks the downstream AngII receptor (AT1) rather than AngII production but produces similar results. Some sources report adding an ARB once maximal ACEi benefit is reached; however, hyperkalemia is one dangerous threat.


Non-steroidal anti-inflammatory drugs (NSAIDs): Indomethacin is the most common drug reported in the literature, although ibuprofen is also described. NSAIDs inhibit prostaglandin (PG) synthetase and, therefore, PG production. PGs are renal vasodilators. Decreased PG production leads to unopposed vasoconstriction of the renal arterioles (afferent >efferent), leading to decreased GFR and reduced proteinuria. The effect has been described as reversible, although underlying kidney disease and baseline GFR play a role in the duration of the effect.


A recent retrospective case series describing ACEi and NSAID therapies in children concluded that ACEi is the drug of choice for MN due to its lower side effect profile.


Calcineurin inhibitors (CNIs) are rarely used for MN, and the effect may be reversible. The MOA is dose-dependent vasoconstriction of arterioles (afferent>efferent), likely through modulating endothelin action.


Metallic Salts, like mercaptomerin sodium (mercury), are no longer used for MN; however, their use is interesting from a historical perspective. Mercury poisoning was one of the first recognized causes of AKI in cases of suicide attempts, and it makes sense that we can use mercury to reduce GFR. The MOA is by injury of the juxtaglomerular cells, thereby reducing renin production. In addition to tubular necrosis (due to decreased renin), it can also cause neurologic disease (“mad as a hatter”).


Monitoring for any MN therapy includes:

  • Blood pressure (BP)

  • Serum albumin

  • Urine output

  • Urinary protein (protein to creatinine ratio or total protein/day)

  • Chemistries (Serum creatinine, BUN, potassium, and in the case of NSAIDs, liver function tests)

As with any treatment, there is a chance of treatment failure or intolerance to the medication necessitating cessation. If there is no progressive improvement in proteinuria, continuing to increase the dose of your agent may increase side effects. At this point, consider adding or switching to another agent if BP and labs allow or seek alternatives to medical nephrectomy.


Complications of native kidney nephrectomy


Surgical Nephrectomy: Apart from the common complications of surgical procedures, such as infection, pain, and bleeding, surgical nephrectomies can lead to urinary tract infection, hematuria, and acute kidney injury. Unilateral nephrectomies increase the risk of chronic kidney disease (CKD) due to hyperfiltration injury that manifests as proteinuria, HTN, and nephrosclerosis.


Renal Artery embolization: A critical complication is “post-infarction Syndrome” or “post-embolization syndrome,” characterized by fever, nausea, vomiting, leukocytosis, and flank pain. The pain can be severe enough to warrant a nerve block. The management is mainly supportive (using analgesics, antipyretics, and antiemetics), typically for a few days. This syndrome is one of the reasons for overnight monitoring post-procedure. Other complications include a lower success rate, possibly due to the development of collateral vessels and injury to the vasculature, which may cause difficulty with transplant anastomosis.


Ureteral Ligation: Complications include painful hydronephrosis and infection, although a series in adults showed no increased risk for infection over surgical nephrectomy.


Medical Nephrectomy: Most complications associated with medical nephrectomy are secondary to the side effects of medications used for reducing GFR. Therefore, close monitoring is essential!

  1. Side effects of RAASi: Hyperkalemia, marked rise in serum creatinine, and hypotension (often what limits therapy escalation). In addition, bradykinin syndrome (dry cough, angioedema, etc.) due to inhibition of bradykinin and substance P degradation is seen with ACEi. Hypotension caused by ACEi may be mitigated by stopping other antihypertensives or lowering the ACEi dose.

  2. Side effects of NSAIDs: Gastritis, hepatic impairment, hyperkalemia, and HTN (related to salt and water retention).

  3. Side effects of CNI: Hyperkalemia, HTN, diabetes, gingival hyperplasia, hirsutism, and more, depending on the type of CNI.

Figure 4. Short-term and long-term complications following native kidney nephrectomy.

Outcomes of native kidney nephrectomy:

Outcomes for pediatric patients undergoing nephrectomy depend on the modality used (surgical vs. medical, unilateral vs. bilateral, etc.). Bilateral nephrectomies will necessitate KRT, which includes dialysis and/or transplant. Medical nephrectomy can have varying rates of success, and some methods may have the return of urine output and proteinuria when medication is discontinued. Studies revealed that in patients with a history of unilateral nephrectomy (for oncologic cases like Wilms Tumor and non-oncologic cases like trauma or a non-functioning kidney from Vesico Ureteric Reflux), an increased risk of decreased GFR, proteinuria, and HTN, particularly after 30 years of age. This increased risk can be attributable to pre-existing kidney damage, low nephron endowment in the preserved kidney, or compensatory hyperfiltration.


Graft nephrectomy (GN)

Definition: Surgical or non-surgical removal of the failed kidney allograft is graft Nephrectomy. Minson et al. observed that over half of failed pediatric kidney allografts undergo graft nephrectomy. A failed allograft is hypothesized to incite a chronic inflammatory reaction, which subsequently causes increased ferritin, decreased erythropoiesis, hypoalbuminemia, and allosensitization. At times, failed allografts can provoke graft intolerance syndrome, characterized by abdominal pain, fever, gross hematuria, and enlarged allograft.


Graft Nephrectomy is likely to minimize HLA sensitization, which improves the chance of future re-transplant. Conversely, the graft may act like a sponge and absorb circulating donor-specific antibodies (“sponge-effect”), thereby preventing antibody appearance in the circulation. Inherent properties of the antibodies absorbed by the graft differ from those that remain in circulation as they do not activate complement but possess a greater ability to block complement-fixing antibodies attached to the cellular targets. Allograft nephrectomy might produce rebound HLA and Donor specific antibodies. Hence the decision for GN and continuing immunosuppression needs to be individualized.


Indications: There are absolute and relative indications of graft nephrectomy, as illustrated in the infographic (Figure 5).


Figure 5: Indications for graft nephrectomy


Techniques: There are surgical and non-surgical methods of graft nephrectomy.


Surgical methods include intraperitoneal and extraperitoneal approaches as outlined below in figure 6.


Figure 6:


Renal artery embolization (RAE) is a non-surgical, minimally invasive alternative to surgical graft nephrectomy. Devascularization of the allograft is achieved by percutaneous puncture of the femoral artery, and graft thrombosis is induced using ethanol, stainless steel coils, or Tris acryl microspheres. The major advantage of this procedure is decreased pain, lower incidence of bleeding, and reduced length of hospitalization. Sometimes RAE is used as a neo-adjuvant intervention where embolization is done one or two days before graft nephrectomy to minimize postoperative complications.


Complications of graft nephrectomy: In addition to difficulties similar to native nephrectomy, specific surgical complications post graft nephrectomy include major hemorrhage, sometimes necessitating ligation of the external iliac artery, postoperative ileus, bowel obstruction, lymphoceles and incomplete removal of graft tissue. Complications following renal artery embolization include post-embolization syndrome, necrotizing pyelonephritis, renal artery embolization, coil migration with limb embolization, and arterial pseudoaneurysm.


Figure 7: Pros and cons of graft nephrectomy

Outcomes: Zerouali et al. studied the outcomes of graft nephrectomy in children. Short-term complications include wound infection, deep vein thrombosis, and lower respiratory tract infections. Long-term allosensitization outcomes and panel reactive antibodies were analyzed by Sener et al., which observed that early graft nephrectomy (within six months of KT) aids in limiting allosensitization and decreased panel reactive antibody levels compared to late graft nephrectomy.


Immunosuppression post-graft nephrectomy: The evidence regarding the cessation of immunosuppression needs to be firmly established. Complete elimination of immunosuppression after graft nephrectomy is an essential prognosticator of allosensitization. In general, children are more likely to undergo retransplantation. Therefore, the risk of sensitization can be minimized by continuing immunosuppression. Furthermore, the intracapsular approach of graft nephrectomy may leave residual graft tissue, necessitating the continuation of immunosuppression. The decision to stop immunosuppression should be individualized based on the child's risk of infection, malignancy, and cardiovascular disease. The British Transplantation Society guidelines recommend cessation of all immunosuppression except steroids, which are withdrawn over time.


Table 1. Methods, indications, and complications of native kidney and graft nephrectomy


Pearls:

  • Nephrectomy can be accomplished through several means, including surgical nephrectomy, renal artery embolization, and medical nephrectomy.

  • Indications for nephrectomy include nephrotic syndrome with severe symptoms (fluid overload, severe malnutrition), malignancy, trauma, living donation, and others.

  • Close monitoring for medical nephrectomy is necessary to detect harmful side effects that require discontinuing the therapy, such as hypotension.

  • Graft Nephrectomy in children is a viable option where benefits preponderate the risks in consideration of retransplant in the future.

AcademicCME (www.academiccme.com) is accrediting this educational activity for CE and CME for clinician learners. Please go to https://academiccme.com/kicr_blogposts/ to claim credit for participation.


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